MANUAL OF PEDIATRIC NEPHROLOGY

2nd Edition

2002

For Residents in the DM Paediatric Program

UWI

© Maolynne Miller
To: The Residents

This manual, like the first edition (1988), is dedicated to the hardworking residents in the
DM Paediatrics programme who have been my inspiration throughout the years. I hope it
will be helpful to them in their preparation for paediatric practice, especially in territories
which have no paediatric nephrology services.

I wish to thank the residents who helped with this manual, in particular Dr. Klaas
Wierenga whose computer expertise was indispensable, and Dr. Young who
painstakingly graduated the peritoneal dialysis bags.

This manual has been prepared as a printed record of paediatric nephrology lectures
given over the last two years, and is not intended for commercial distribution. Any cost
affixed to the manual is solely to cover the printing expenses, and not for personal profit.

Every attempt has been made to avoid any errors, but in spite of this, it is possible that
some may have occurred. If any aberrations are noted, please check other references and
bring the matter to the author’s attention.

Thank you.

Maolynne Miller. M.B.B.S., F.R.C.P.(C).

January 2002

2
3
 TABLE OF CONTENTS

Chapter Title Start page

1 Assessment of renal function 5
2 Red urine and haematuria 19
3 Proteinuria 23
4 Acute glomerulonephritis 27
5 Nephrotic syndrome 33
6 Disorders of water and electrolyte balance 38
7 Urolithiasis and disorders of calcium balance 50
8 Urinary tract infections 57
9 Enuresis and other voiding disorders 62
10 Acute renal failure 71
11 Acute peritoneal dialysis 83
12 Chronic renal failure 89
13 Hypertension 95
14 Disorders of acid – base balance 106

4
 CHAPTER 1

ASSESSMENT OF RENAL FUNCTION

GLOMERULAR:
Fluid balance : fluid balance, edema
Filtration : wastes - urea, creatinine, creatinine clearance, electrolytes
water - edema, dilutional hyponatremia - electrolytes, specific gravity, osmolality
red cells - urine microscopy
protein - spot urine protein/creatinine, 24 hour urine protein
urinalysis - Labstix/ Uristix - sulfosalycilic acid
Radiology

TUBULAR:
Urine concentrating ability - specific gravity, osmolality
Acid/base balance - urine pH, serum bicarbonate, blood gases
Electrolyte and calcium balance - Na, K,Cl, PO4,Ca - blood and urine
+/- alkaline phosphatase(Alk.phos), serum albumin

ENDOCRINE:
1- hydroxylation of 25 OH vitamin D - Ca, PO4, Alk. phos, albumin
- X ray ( L) wrist - bone age
- X ray (L) hand - penetrated view for renal osteodystrophy
Renin - Blood pressure, electrolytes, plasma renin activity
Erythropoietin - Hb, reticulocyte count
**************************************
HISTORY:
Growth, haematuria, oedema, urinary stream, dysuria, oliguria;
Family history, syndromes

EXAMINATION:
Mucous membranes, growth parameters, edema, blood pressure, abdominal organomegaly, genital
anomalies.

URINE:

Appearance
Pale to dark yellow (normal), red (blood or beets), green (bilirubin), brown or black (old blood or
myoglobin), purple (porphyria). Salmon coloured powder on diaper (amorphous urates), frothy
(proteinuria), clear and colourless (dilute urine).

Microscopy (see Figure 1)

Uncentrifuged - low power (X 40), and high power (X 500), for epithelial cells, WBC, bacteria, RBC (if
haematuria gross).
Centrifuged - best for RBC, casts, WBC. Ideally 10 - 15 mls freshly voided urine centrifuged at 2000 rpm
for 5 minutes. Invert the tube to remove supernatant and examine residual sediment on a glass slide.
Normal microscopy - < 5 rbc/high power field (HPF)
< 5 wbc/ HPF
Hyaline casts and assorted crystals

5
 Figure 1 – Microscopic urinary findings

Urine concentrating ability -

Best assessed on first voided morning urine sample after an overnight fast. Urine should be voided before
retiring the previous night.
Tested by - urine osmolality (UOsm) and urine specific gravity (Usg).
a) Urine osmolality (measured by freezing point depression method).
Normal maximal urine osmolality (max UOsm)
Age Max UOsm (mOsm/kg H2O)
Neonate 600 - 700
Child or adult 800 - 1200

Calculate UOsm from Usg as follows: UOsm = (Usg - 1.000) X 40,000 mOsm/kg H2O
Serum Osm = (2 serum Na) + glucose (mmol/l) + urea (mmol/l)
Hospital for Sick Children Residents Handbook of Pediatrics (1987), 7th edition, p 130. Abelson and Smith

b) USG
Measured by a) refractometer (1 drop of urine) or b) hygrometer (several mls of urine).
Less accurate but more convenient than UOsm. Falsely elevated by - high molecular weight substances
e.g. glucose, protein, radio opaque dyes and mannitol

1 gm glucose/dl in urine - increases USG by .003

1 gm protein/dl in urine - increases USG by .003

6
 In chronic renal failure USG = 1.010 (UOsm 300mOsm/kg H 0)
In diabetes insipidus USG < 1.005

URINALYSIS
PROTEIN may be detected - qualitatively by - dipstix (Albustix , Labstix) or
- 3% Sulfosalicylic acid
quantitatively by - timed urine collection
- spot urine protein/creatinine ratio
Dipstix - colour change reflects protein content of urine. i.e. yellow (no protein) to dark green (4+
proteinuria). False positive - alkaline urine. False negative - dilute urine.

3% Sulfosalicylic acid(SSA) method:

Add 0.5ml 3% SSA to 0.5 ml urine in a test tube. The resultant turbidity reflects degree of proteinuria
(see below). False positives - concentrated urine, penicillin, gantrisin, cephalosporins, p Amino -salicylic
acid.
_____________________________________________________________________________
Urine Reaction Interpretation
Protein concentration (g/l) (place print behind test tube)
_____________________________________________________________________________
<5 clear negative

5 - 10 very faint turbidity-(coconut water) trace

can read print

10 - 30 turbid - can see line only 1+

30 - 100 white cloud - can't see line 2+

100 - 500 white cloud with fine precipitate 3+

> 500 flocculent precipitate 4+

_____________________________________________________________________________
For home monitoring by out patients - cloudy urine = significant proteinuria (> 2+), and may herald a
relapse of nephrotic syndrome. Clear urine = trace/ negative proteinuria. Proteinuria < 1+ is normal.

BLOOD - may be detected by urine microscopy (only reliable method) and suggested by the Hemastix.
Hemastix also tests positive for blood with myoglobinuria or hemoglobinuria .

pH - determined on a fresh urine sample by dipstix method (accuracy of +/- 0.5 pH units) or by pH
meter on special arrangement with Chemical Pathology (more accurate).

REDUCING SUBSTANCES - not usually present in urine

Clinistix or Dipstix - positive for glucose. Clinitest method - positive for all reducing sugars -
glucose, galactose, fructose, lactose and other non glucose reducing substances.
Clinitest method - 2 drops urine to 10 drops water, then add clinitest tablet. Colour depends on amount
of reducing substance present.
Colour [Glucose] Colour [Glucose]

blue - negative green - brown - 1%

blue - green - trace yellow - 2%
green - 0.5% yellow - orange - 3%
orange - 5%

7
24 HOUR URINE COLLECTIONS
To assess completeness of the collection, always measure on the same collection, the 24-hour creatinine
excretion.
24 hr urine CREATININE = 135 - 175 µmol/kg/dy (adult female or child)
= 175 - 220 µmol/kg/dy (adult male)

IF RESULT IS < THE ABOVE VALUES, THE COLLECTION IS INCOMPLETE AND THE RESULTS
THEREFORE UNRELIABLE

CREATININE CLEARANCE AND GLOMERULAR FILRATION RATE (GFR) - Both are

indices of glomerular function

Creatinine Clearance (CCr) - measured

-based on timed urine collection ( usually 24 hours )
- may be falsely high when renal function markedly reduced as creatinine secretion occurs
-fairly good measure of GFR if collection complete

Calculation of CCr (from 24 hr urine)

CCr = uCr X V X 1.73 = mls/min/1.73 m2
pCr X t SA

uCr = urine concentration of Creatinine (µmol/l)

pCr = serum concentration of Creatinine (µmol/l)
V = urine volume in timed interval (usually 24 hrs) (ml)
t = time of collection of urine (24 hr = 1440 mins) (min)
SA = surface area derived from height and weight

ESTIMATED GFR * - from plasma creatinine, and height

GFR = Ht (cm) X k (ml/min/1.73m2)
pCr(µmol/l) X .0113

GFR = glomerular filtration rate (ml/mim/1.73m2) Ht = height (cm)

pCr = plasma or serum creatinine (µmol/l)
k = constant of proportionality , a function of urinary creatinine per unit of body size ; may vary
from the mean in malnutrition or obesity

Mean k* values at different ages

Age group (years) k
low birth weight infants < 1yr 0.33
full term infants < 1yr 0.45
children 2-12 0.55
females 13 -21 0.55
males 13-21 0.70
____________________________________________________
*From "The use of plasma creatinine concentration for estimating glomerular filtration rate in infants,
children and adolescents" Pediatric Clinics of North America (1987 ) 34 : 582

CREATININE CLEARANCE (cCr) FROM LABORATORY VALUES

Laboratory units are mls/min
Convert to mls/min/1.73m2 as follows :
cCr = (mls/min) X 1.73 = mls/min/1.73m2
2
body surface area (m )

8
NORMAL CREATININE CLEARANCE FOR AGE > 2 YEARS SHOULD BE > 90 ml/min/1.73m2
NORMAL SERUM CREATININE (µmol/l) for age over 5 years = (< age in years X 10)
For age < 5 years = < 50µmol/l

NORMAL GFR AT DIFFERENT AGES ADJUSTED TO 1.73 m2

Age GFR(ml/min/1.73m2 ) Range (+/- 2SD)

Premature 47 29 -65
2-8 days 38 26-40
4-28 days 48 28-68
35-95 days 58 30-86
1-5.9 months 77 41-103
6-11.9 months 103 49 -157
12-19 months 127 63 - 191
2-12 years 127 89 -165
Adult males 131 88 -174
Adult females 117 87 -147
________________________________________________________________________
From Pediatric Nephrology (Page 288, 1987 Edition), Holliday, Barratt, Vernier -Editors; Williams and
Wilkins -Publishers.

NORMAL 24 HOUR URINE VOLUME

(usually 2 -2.5 ml/kg/hr)
Age Volume (mls) .
1 - 2 days 30 -60
3 - 10days 100 -300
10 - 28 days 250 -450
2mo - 1 year 400 -500
1 - 3 years 500 -600
3 - 5 years 600 -700
5 - 8 years 650 -1000
8 - 14 years 800 – 1400

Bladder data:
Bladder capacity (mls)
Children < 2 years : bladder capacity (ml) = 7 X weight (kg)
Children 2 – 11 years : bladder capacity (mls) = (age (years) + 2 X 30)
(Urology 21:248, 1983 – From Urological Clinics of North America, 1995, 22: 205 –219)
or bladder capacity = (age years +2 ) ounces

Residual volumes:
Age < 1 year usually 5 – 10 mils
School children usually < 5 mls

(J Urol 1989; 141: 916 –917, Scan J Urol 1976; 37 (Suppl): 1- 106 - From Ped Nephrology 1999 edtn.)

Water losses with fever:

Fever increases water loss by 7mls / kg/day for each oF rise in temperature above 99oF , or
10 ml/kg/day for each oC rise above normal (37 oC)

9
Spot urine protein/ creatinine:
Protein (mg/l X .1) = mg/dl
Urine creatinine (µmol/l) X0.0113 = mg/dl

Normal < 0.2 Minimal proteinuria 0.21 – 0.5

Moderate proteinuria 0.51 – 2.0 Nephrotic range > 2.0

Tubular reabsorption of phosphate = 1 - [U / P phos mmol/l ] x100%

[U/P creatinine µmol/l]
Normal > 80 % Low values suggest secondary hyperparathyroidism

Spot urine electrolyte values

Spot urine Na and K values should be interpreted in relation to serum values. Spot urine Na and K should be
< 5 – 10 mmol in the face of hyponatremia and hypokalemia respectively. If spot urinary losses exceed this,
suspect the kidney as being the source of the serum abnormality.

Normal solute / creatinine ratios

Calcium(mmol/l): creatinine(µmol/l)= <.00074 If increased = hypercalciuria
Uric acid(mmol/l):creatinine(µmol/l)= <.00067 If increased = hyperuricosuria

For normal 24 -hr urinary solute excretion see Chapter 7

24 urine phosphate 3.87 – 6.46

Transtubular potassium gradient (TTKG) - mineralocorticoid effect

TTKG = UK // U/ P Osm
SK
SK (serum potassium) (mmol/l)
U Osm – urine osmolality (mOsm/kg H20)
POsm - plasma osmolality (mOsm/kg H2O)

> 6 = mineralocorticoid effect

< 4.9 (infant) = reduced mineralocorticoid effect
< 4.0 (child) = reduced mineralocorticoid effect

RENAL IMAGING
Renal ultrasonography
Assessment of renal anatomy – measurement of renal size, detection of obstruction, cysts, renal or perinephric
abscesses. Hyperechogenicity suggests renal parenchymal disease. Advantage- no radiation.
Disadvantage -Is not sensitive for the detection of pyelonephritis, renal scarring and cannot reliably exclude
vesico-ureteric reflux – VUR. Ask for renal measurements and compare with normal values (see below). For
premature infants request transverse renal measurements as well.

Normal renal lengths vs age – Table 1

Normal renal lengths vs age, weight, height and BSA – Figure 1
Normal renal measurements – transverse diameter for premature infants (Table 2)

10
Table 1. AGE-RELATED MEAN RENAL LENGTHS BY ULTRASONOGRAPHY
Adapted from: American Journal of Roentgenology 142: March, 1983

Mean Renal Length

Average age* Interval* (cm) SD**
0 mo 0-1 wk 4.48 0.31
2 mo 1wk-4 mo 5.28 .66
6 mo 4 -8 mo 6.15 .67
10 mo 8mo-1 yr 6.23 .63
1 1/2 1-2 6.65 .54
2 1/2 2-3 7.36 .54
3 1/2 3-4 7.36 .64
4 1/2 4-5 7.87 .50
5 1/2 5-6 8.09 .54
6 1/2 6-7 7.83 .72
7 1/2 7-8 8.33 .51
8 1/2 8-9 8.90 .88
9 1/2 9-10 9.20 .90
10 1/2 10-11 9.17 .82
11 1/2 11-12 9.60 .64
12 1/2 12-13 10.42 .87
13 1/2 13-14 9.79 .75
14 1/2 14-15 10.05 .62
15 1/2 15-16 10.93 .76
16 1/2 16-17 10.04 .86
17 1/2 17-18 10.53 .29
18 1/2 18-19 10.81 1.13

* Years unless specified otherwise ** +/- 2SD is normal

11
Figure 1 - Normal renal lengths versus age, weight, height and BSA

From: Han BK & Babcock DS. Sonographic Measurements and Appearance of normal kidneys in
children. AJR (1985) 145:611-6

12
Table 2 - Fetal kidney by gestational age group in normal fetuses

Gestational Fetal kidney Fetal kidney Fetal kidney

Age measurements measurements measurements
(wk) anteroposterior (cm) transverse (cm) circumference (cm)

Mean (SD) Mean (SD) Mean (SD)

<16 0.84 (0.24) 0.86 (0.14) 2.79 (0.64)

(n=9)

17-20 1.16 (0.24) 1.13 (0.25) 3.80 (0.72)

(n=18)

21-25 1.49 (0.37) 1.64 (0.40) 5.40 (0.68)

(n=7)

26 –30 1.93 (0.19) 2.00 (0.28) 6.58 (0.67)

(n=11)

31 –35 2.20 (0.32) 2.34 (0.42) 7.86 (0.86)

(n=19)

>36 2.32 (0.32) 2.63 (0.50) 8.42 (1.39)

(n=25)

Adapted from American Journal of Obstetrics and Gynaecology (1980) Vol 136: 253
Assessment of fetal kidney size in normal gestation by comparison of ratio of kidney circumference to
abdominal circumference (Grannum, Bracken, Silverman, Hobbins)

Nuclear scanning
1. Detection of acute pyelonephritis, renal scarring – 99mTc DMSA, Glucoheptonate
2. Assessment of renal function and differential renal function – 99m Tc DTPA and glucoheptonate, 51
Cr EDTA scan, 99m Tc MAG3
3. Differentiation of obstructive from non obstructive uropathy – diuretic renography – DTPA and
glucoheptonate
4. Detection of vesico- ureteric reflux – direct and indirect cystography
5. Screening test for renal artery stenosis (Captopril enhanced renography) – see Chapter 13
(Hypertension)

Types of nuclear scans:

1. 99m Tc DTPA - 99m Technetium labeled diaminotetraethyl pentacetic acid (DTPA) determine renal
morphology and GFR
2. 99m Technetium – labeled dimercaptosuccinic acid (DMSA) scan – detect renal scarring
3. 99m Tc Glucoheptonate renal scan – detect renal scarring and assess renal function
4. 51 Cr EDTA scan determine GFR
5. 123 I OHI – iodine labeled orthoiodohippurate – measures renal plasma flow – excellent renal imaging
6. 99m Tc MAG3 –Technetium labeled mercapto acetyl glycylglycine –measures effective renal plasma
flow (ERPF) – (the proportion of the renal plasma flow presented to the renal secretory tissue) and
renal function - excellent renal imaging – expensive.

13
Diagnosis and imaging of acute pyelonephritis (AP) and renal scarring - DMSA or glucoheptonate
scans:
After IV injection 99m Tc-DMSA is taken up by the tubular cells in the cortex. Uptake of DMSA is
dependent on blood flow and intact tubular cell function. AP causes local ischaemia and tubular
dysfunction, so involved areas have decreased uptake of the DMSA.
AP- focal, multifocal, or diffuse areas of decreased tracer uptake in the kidney without volume loss.
Scarring - areas of decreased uptake with volume loss.
Cortical scintigraphy should be performed in children with febrile UTI or those in whom AP is a
possibility, even if there is no demonstrable reflux on the cystogram.

Contrast – enhanced computed tomography (CT)-

1. Diagnose acute pyelonephritis –low areas of attenuation in the kidney.
2. CT delineates the perinephric space, and is the study of choice in suspected renal or perinephric abscess
(though ultrasound helpful)
3. Diagnose mass lesions / trauma to kidney
4. Can also assess renal function, but iodinated contrast required – allergic risk.

CYSTOGRAPHY
Type of cystograms:
1. Fluoroscopic voiding/ micturating contrast radiography (VCUG / MCUG)
2. Radionucleide (isotope) cystogram (RNC).

MCUG - - very good anatomical resolution – highly detailed images of bladder and urethra. Urethral
imaging essential in boys to exclude posterior urethral valves, detect bladder wall abnormalities eg
trabeculation, diverticula, and ureterocoeles. – accurate grading of reflux using the International
Classification I- V.
1. Boys - first time work up of UTI – urethral evaluation
2. Patients with history of voiding dysfunction – to evaluate bladder function

Radionucleide cystography –
1. Very sensitive for detection of reflux, because the entire bladder cycle from filling to after voiding is
continuously monitored.
2. Lower spatial resolution than the MCUG so bladder wall abnormalities may be missed. In addition, the
urethra cannot be evaluated.
3. Advantage - lower radiation.
4. Post op follow - up and for screening of asymptomatic siblings of patients with VUR (male or female)
5. Possibly for initial evaluation of girls with UTI because urethral anomalies are rare and significant
bladder wall abnormalities may be detected on ultrasonography.

Indirect nuclear cystography –

1. Observed on voiding at the end of the DMSA or glucoheptonate scan.
2. More sensitive than voiding cystography and direct radionucleide cystography in detection of
VUR.
3. Can only be preformed in children who can void on request

Direct nuclear cystography –

1. Less radiation than the standard fluoroscopic MCUG.
2. Use for follow – up of VUR

14
Timing of cystography–
After antibiotic therapy has begun and the urine is sterile. It is not necessary to wait a prolonged period
after treatment. In patients with dysuria or other cystitis symptoms, wait until asymptomatic so adequate
bladder filling may occur. Underfilling of the bladder may result in a false negative result for VUR.

Diuretic renography –(DR) (request renal glucoheptonate scan with Lasix)

1. Imaging modality used to differentiate obstructive from non obstructive hydronephrosis / hydroureter
(H/H)
2. Performed using 99m Tc- DTPA or 99m TC MAG3 or glucoheptonate. After injection of the agent
sequential images of the kidney are obtained. Following excretion and maximal filling of the dilated
collecting system or ureter with radioactive tracer, furosemide is injected intravenously (1mg/kg) and
imaging continues. Differential renal function is calculated. The drainage pattern of each kidney is
interpreted using the images and washout half times calculated from computer- generated furosemide
washout curve. In obstruction there is delayed or no washout. In dilatation without obstruction there is
good washout with furosemide.

Intravenous urography (IVU)

For renal structure, and function. Cannot be used in severe renal failure as dye is not excreted and is of
limited usefulness in the neonate as excretion is poor.
Normal kidney length on IVU is 3.5 to 4 vertebral bodies and the sizes of each do not differ by more than
1.5 cm

Retrograde and antegrade pyelography – to evaluate the non functional and possibly obstructed kidney

Renal angiography – detect malformations of renal vessels, measure renal vein and vena caval renin in the
evaluation of hypertension

Histology – renal biopsy for histological evaluation of renal parenchymal disease.

15
 BLOOD INVESTIGATIONS

Urea, creatinine, electrolytes, bicarbonate, calcium, phosphate, serum proteins, alkaline phosphatase, uric acid.
Hb. Blood urea is less accurate than creatinine for assessing renal function as it may be increased by many non
renal factors e.g gastrointestinal bleeding, steroids, high protein diets, an reduced in prolonged malnutrition.
Normal values vary with age, sex and size. At birth the urea and creatinine reflect maternal values, but fall to
the paediatric range by 2 weeks.

NORMAL VALUES

Acid -Base status (Blood Gases)

PH Arterial Venous
Newborn 7.33- 7.49 -
1 day 7.25- 7.43 -
2 days – adult 7.35- 7.45 7.32- 7.42

PCO2 Birth – 2 years 26 – 41mmHg

2 years – adult 33 – 46mmHg 40 – 50mmHg

PO2 Newborn 65 – 76mmHg

(room air) Child – adult 80 – 100mmHg 25 – 47mmHg

Actual
Bicarbonate
Newborn 17 – 24mmol/l
2 months – 2 years 16 – 24mmol/l
Child 18 – 25mmol/l
Adult 18 –29mmol/l

Plasma Bicarbonate (not by blood gases)

Age Plasma Bicarbonate (mmol/l)

Term neonate 21 – 23
Preterm neonate 19 – 22
Infants 18 - 22
Children 20 – 26

From Pediatric Nephrology (1987 edition) Holiday, Barratt, Vernier-Editors, Williams

and Wilkins – Publishers ( pages 288, 927)

Phosphate (Phosphorus) (mmol/l) Serum Calcium (mmol/l)

Age Phosphate Calcium (total)

Birth – 1 mo 1.62 - 3.10 Premature (birth – 7 days) 1.75 –2.5

1 – 4 mo 1.55 – 2.62 Term (birth – 7 days) 1.8 – 3.0
4 mo – 1 yr 1.30 – 2.20 Child 2.25 – 2.74
1 – 4 yr 1.16 - 2.10 Adult 2.12 – 2.62
4 – 8 yr 1.16 – 1.81
9 – 14 yr 1.07 – 1.71 Calcium (ionized, free) (mmol/l)
> 14 yr 0.87 – 1.53 > 1 month – adult 1.0 – 1.35

16
Correction of serum calcium for hypoalbuminaemia: (2 methods)
• For every 10 g/l serum albumin is below normal (40g/l), serum calcium rises by 0.2 mmol/l
e.g. serum alb = 20g/l, measured serum Ca = 2 mmol/l , true serum Ca = 2.4 mmol/l or

• True serum calcium mmol/l = [measured serum calcium (mmol/l) - serum albumin (g/l) ] + 1
[ 40 ]

Alkaline phosphatase – produced by bone, liver, kidney, intestinal mucosa

Male Age Alkaline phosphatase (IU/l ) Female Age

(years) Males Females (years)
_____________________________________________________________________
<1 175 – 600 185 – 555 <1
1–8 175 – 400 185 –520 1–2
9 – 11 180 - 475 185 – 425 3–8
12 – 15 200 – 630 160 – 500 9 – 13
16 – 17 100 – 455 90 - 400 14 – 15
18 – 19 80 – 210 45 – 140 16 – 18
> 19 60 – 150 25 – 100 > 18

Potassium (mmol/l or mEq/l) Sodium (mmol/l or mEq/l)

Premature infants 4.5 – 6.5 Premature infant 132 - 140

Term infants 5.0 – 6.5 Term infant 133 - 142
2 days – 2 weeks 4.0 – 6.4 Child 135 - 143
2 weeks – 3 months 4.0 – 6.2 Adult 135 - 145
3 months – 1 year 3.7 - 5.6
1 – 16 years 3.5 – 5.2

Correction of serum sodium for hyperglycaemia:

True serum Na (mmol/l) = measured Na (mmol/l ) + blood glucose (mmol/l ) X 1.5
5.5

Creatinine (µmol/l). Serum creatinine is reduced in malnourished or small children. In general, the normal
serum creatinine (µmol/l) is < [age (yrs) x 10], eg normal Creatinine for a 9 yo is < 90µmol/l)

Age (yr) Creatinine Urea (mmol/l)

<5 < 44
5–6 < 53 Age Urea .
6–7 < 62 Newborn 2.9 - 10
7–8 < 71 1 – 2 years 1.8 – 5.4
8–9 < 80 2 – 16 years 2.9 – 7.1
9 – 10 < 88
> 10 < 106
adult male <122
adult female < 101

Uric acid (mmol/l)

Any age 0.2 – 0.47

17
 Figure 2 Body surface area nomogram for Figure 3 Body surface area nomogram for infants
children and adults (From Haycock GB, (From Haycock GB, Schwartz GJ, Wisotsky DH. J
Schwartz, Wisotsky DH. J Pediatr 1978; 62 –66) Pediatr, 1978; 93: 62 –66)

References:
1. Pediatr Clin N Am 1997, 44:1065 – 1089 – Imaging in pediatric urology
2. Am J of Roentgenology 1986, 145: 611 – 616 – Sonography of kidneys in children
3. Pediatr Nephrol –TTKG ref (journal)
4. J Pediatr (1990) 116: 243-247 for spot urine prot/creat reference
5. Urolog Clin N Am 1995, 22: 205 – 219, 1 - 20
6. Pediatric Nephrology, 2nd Edition (1987). Holiday , Barratt, Vernier- editors, Williams and Wilkins –
publishers -926 –928, 282 – 299
7. Resident’s Handbook of Pediatrics –7th Edition (1987). Abelson and Smith - Hospital for Sick Children-
735 - 797
8. Pediatric Nephrology, 4th Edition,(1999)– Barratt, Avner and Hammond-Editors. Clinical methods:
Chapters 18-22, pages 317-390
9. Ped Clin N Am 1987, 34: 571 – 589, Use of plasma creatinine for estimating glomerular filtration rate in
infants, children, adolescents –Schwartz et al
10. Manual of Nephrology –Diagnosis and Therapy – 3rd Edition, 1980. Shrier RW.
11. Contemporary issues in nephrology – Vol 25, 1992 Diagnostic techniques in renal disease (305 –330)
12. TTKG reference – Pediatr Nephrol (1990) 4: 105 -110

18
 CHAPTER 2

RED URINE and HAEMATURIA

Haematuria
Definition:
>5 rbc/ hpf on microscopy of the sediment of a freshly voided urine centrifuged at 1500 – 3000 rpm for 5
minutes
The diagnosis can only be made by urine microscopy
Not all red or dark urine is true haematuria

Evaluation of patient with “red “ urine

Test with Hemastix/ Labstix

+ blood no blood

centrifuged microscopy pigments

External- drugs, dilantin, pyridium, rifampin,

senna, beets
< 5 rbc /hpf numerous rbc Internal – pink diaper syndrome (urates)
red diaper syndrome (Serratia)
Myoglobinuria true haematuria bilirubin (yellow-brown)
porphyrins (red)
OR OR alkaptonuria (black)

Haemoglobiuria external contamination

of urine with blood

Centrifuge patient’s blood

Clear serum pink serum

Myoglobinuria haemoglobinuria
(haemolysis)

Idiopathic Drugs – quinine, sulphonamides

Chemicals – carbon monoxide
Fava beans, chloroform
Exercise, cold, intravascular haemolysis

Traumatic

19
 TRUE HAEMATURIA

Microscopy

RBC, WBC, bacteria UTI likely

RBC

Crenated Not crenated

Glomerular Non-glomerular

Proteinuria absent

> 2+ with gross haematuria non glomerular

> 1+ with micro haematuria

present usually painful

glomerular bright red
(rbc casts, smokey urine, painless)

Renal/bladder ultrasound
Abnormal - tumour, obstruction, calculus, clots
Normal - usually non surgical haematuria

Renal function
Abnormal >>>> renal biopsy >>> glomerulonephritis (GN)
Normal >>> check family history
Family history of haematuria/renal disease
>>> present >>> possible renal biopsy (GN)
>>> absent >> exclude hypercalciuria / coagulopathy

Pattern of haematuria
Persistent >>>> ? renal biopsy for GN
Recurrent >>>> ? IgA nephropathy (gross haematuria coincidental with URI) >>>> observe

Adapted from Pediatric Nephrology 4th Edition 1999, pg 317 – 318 Editors Barratt, Avner and Harmon

20
Haematuria: aetiology
:
Renal:
• trauma, stones, Berger’s ( IgA nephropathy), benign essential haematuria
• sickle haemoglobinopathy – AS, SS, Sβthal, - acute papillary necrosis
• cysts, tumour
• haemangioma, AV malformation

Non- renal (usually painful)

• Trauma to genitourinary system
• Stones, hypercalciuria, UTI, hyperuricosuria
• Lesions of external genitalia
• Contamination of urine with menstrual or rectal blood

Systemic disease: Coagulopathy – haemophilia V111, 1X, drugs – heparin, coumadin, Vit K deficiency;
thrombocytopoenia – ITP, drugs eg cyclophosphamide

3 tube test (Gross haematuria)

• Initial haematuria (first tube) – distal urethra, urethritis, meatal stenosis
• Terminal haematuria (third tube) – posterior, bladder neck or trigone

History
Symptoms of UTI, glomerulonephritis, trauma, stones. Past history of haematuria, bleeding diathesis,
sickle cell disease /trait. Preceding URI or skin sepsis. Family history of renal disease, haematuria or
deafness or sickle cell disease / trait.

Examination
Growth parameters, BP, temperature, abdomen for masses, trauma, obstructive uropathy, pyelonephritis,
genital area for trauma. Document oedema, skin or throat infection. Actually inspect the diaper for
“blood” – salmon coloured powder which can be scraped from the diaper is amorphous urates. Ask parent
to actually describe the colour and consistency of the material they are calling blood.

Aetiology
In UHWI paediatric population usually acute glomerulonephritis, followed by urinary tract infection
/cystitis, hypercalciuria, trauma , sickle haemoglobinopathy and suspected Ig A nephropathy.

The etiology of haematuria may be determined by the results of urine microscopy and urine tests for
protein. – see algorithms.

Investigations
Investigations depend on likely cause.

General :
Urine microscopy, urine culture, urine test for protein
Hb electrophoresis
Coagulation profile – PT, PTT, platelet count – for gross haematuria
Spot urine calcium: creatinine for hypercalciuria
Mid stream urine for culture and sensitivity

Renal causes:
Blood urea, creatinine and electrolytes, serum albumin, spot urine protein/creatinine if proteinuria
Serum calcium, phosphate, uric acid and alkaline phosphatase if stones suspected
Renal ultrasound – obstruction, cysts. CT scan or IVP for trauma
Test urine of first degree relatives for blood
Renal causes continued:

21
Serology – ASTO, C3, ANF, VDRL, hepatitis B surface antigen – suspected AGN
Immunoglobulins – elevated IgA in some patients with IgA nephropathy / Berger’s disease

In recurrent gross haematuria, renal biopsy is considered if:

• Non glomerular haematuria excluded
• Strong family history of nephritis
• Recurrent gross haematuria and persistent microhaematuria for > 1 year
• Nephrotic syndrome coexistent
• Systemic illness
• Undiagnosed or progressive glomerulonephritis
• Families need for specific diagnosis

Non renal causes –

Investigation depends on suspected cause. Urological referral may be necessary. Refer patients to urology
if haematuria heavy with clots.

Treatment and prognosis depend on the cause.

Familial benign essential haematuria FBEH

• Familial occurrence of microscopic haematuria

• Without proteinuria
• Without progression to renal failure
• Without hearing defect or other extra renal manifestations
• EM diffuse attenuation of glomerular basement membrane (GBM) – thin basement membrane disease
is not a specific diagnosis nor is it specific for FBEH.
• Autosomal dominant
• May be indistinguishable from heterozygotes of autosomal recessive Alport’s syndrome

IgA nephropathy
• Recurrent gross haematuria usually occurring 1 – 2 days after a respiratory tract infection eg sinusitis
or tonsillitis.
• Prognosis variable

Haematuria in the neonate - gross haematuria is rare

• Bleeding tendencies – Vit K deficiency
• Trauma – external meatus, urethra, bladder, post bladder tap, bladder haemangioma
• UTI
• Obstructive / reflux uropathy
• Nephritis – interstitial nephritis – drugs eg aminoglycosides / glomerulonephritis
• Vascular disorders – ATN, corticomedullary necrosis, renal vein thrombosis, adrenal hemorrhage
• Cystic disorders – ARPKD (autosomal recessive polycystic kidney disease), MCDK (medullary cystic
disease of the kidneys, cystic dysplasia
• Tumours – Wilms, mesoblastic nephroma, fetal hamartoma, angioma

References;
1. Pediatric Nephrology (1999) 4th Edition. Barratt, Avner and Harmon Editors: 317-318, 698,700-701,
1053-1054,497 –498
2. Ped Clin N Am (1997) 44:1191 – 1210 – Hematuria
3. A practical primary care approach to haematuria in children. Ped Neph (2000) 14: 65-72

22
 CHAPTER 3

PROTEINURIA

Definition:
• Presence of protein in the urine.
Classification: (temporal)
• Persistent
• Transient
• Intermittent - orthostatic
Classification: (etiological)
• Pre glomerular - (overflow) – excessive protein production exceeding renal tubular absorptive capacity
e.g. Bence Jones proteinuria
• Glomerular - defect in glomerular filtration barrier - glomerulonephritis, microalbuminuria as early
index of glomerular disease in diabetes mellitus
• Post glomerular – (tubular) – failure of absorption of normal filtered low molecular weight proteins
e.g. lysozyme, B2 microglobulin – reflects tubular damage

Normal proteinuria
70% - globulins from the kidney, urinary tract, seminal glands. 30% - albumin.
Tamm Horsfall glycoprotein is formed in the kidney and is the main constituent of matrix of urinary casts
• Trace/negative proteinuria
• Spot urine protein(mg/dl)/creatinine (mg/dl) < 0.2
• 24 hour urine protein < 150 mg/day
• <4mg/m2/hr in 12 –24 hour urine collection

MEASUREMENT OF URINARY PROTEIN

QUALITATIVE:
• Urine dipstick (albustix) – tetrabromophenol blue buffered to alkaline pH to a yellow colour in the
absence of protein. Varying degrees of proteinuria produce increasing shades of green (dark green =
4+ proteinuria).
False positive: concentrated and alkaline urine- pH>8, contamination with chlorhexidine or
benzalkonium
False negative in dilute urine

• 3% Sulphosalicylic acid (SSA) -

Add 0.5cc of 3% SSA to 0.5cc urine in a test tube. The resultant turbidity reflects the degree of proteinuria
(see below).

False positives - concentrated urine, penicillin, Gantrisin, p Aminosalicylic acid, radiographic contrast
agents, suphonamides, tolbutamine, cephalosporins.
False negative in dilute urine

23
Urine testing with SSA (3%) vs Albustix

Urine protein concentration Reaction Albustix

(g/l) (place print behind test tube)
<5 clear negative
5-10 faint turbidity – can read print trace
10-30 turbid – can see black lines 1+
30 -100 white cloud – can’t see black lines 2+
100-500 white cloud – with precipitate 3+
>500 Flocculent precipitate -gel 4+

SEMIQUANTITATIVE
Spot urine protein (mg/dl) .
Spot urine creatinine (µmol/l) X .0113 (= mg/dl)

Normal < 0.2

Minimal proteinuria 0.2 – 0.5
Moderate proteinuria 0.5 –2.0
Nephrotic proteinuria >2

QUANTITATIVE
• Timed urine 12 – 24 hour urine collection

SIGNIFICANT PROTEINURIA
• 1+ on 2 of 3 random urines if urine S.G. < 1.015
• > 2+ if urine S.G. >1.015
• Urine protein/creatinine ratio > 0.2 (on early morning urine)
• 4 – 39 mg/m2/hr in 12 – 24 hour collection
• nephrotic range proteinuria > 40mg/m2/hr in 12 – 24 hr collection
.05g/kg/day in 24 hr collection
urine protein/creatinine >2.0

Significant proteinuria related to age

AGE SIGNIFICANT PROTEINURIA mg/day

(>2SD above mean)
2 – 12 months >155
3 – 4 years >140
4 – 10 years >190
10 – 16 years > 250

Based on weight at 50th percentile for median age category

EVALUATION OF PROTEINURIA
Ideal sample for testing:
• first voided morning urine sample (rule out orthostatic proteinuria)
• after cleaning genitalia (rule out contamination with genital mucous)

PROTEINURIA ALONE IS USUALLY BENIGN

PROTEINURIA WITH HEMATURIA IS ALWAYS PATHOLOGICAL

24
IF RANDOM URINE DIPSTIX PROTEIN > 1+

Test sample with SSA -

a) < 1+ protein /pH >6 = false positive on dipstix
no further investigation or treatment

b) > 1+protein / pH < 6 = positive SSA test for protein

= contamination OR true proteinuria

Positive SSA test

Clean genitalia and collect MSU
a) No proteinuria = false positive = contamination
b) Proteinuria

Proteinuria despite cleaning

a) Culture MSU, urine microscopy (uncentrifuged)
Positive culture / bacteria, WBC on unspun urine
+/- Blood on dipstix
urinary tract infection
b) Repeat test for protein x 2 (total of 3 samples)

c) Test urine for blood (dipstix and centrifuged urine microscopy)

Proteinuria in 1of 3 samples - transient proteinuria- exercise, fever, dehydration

No further investigation

Proteinuria in > 2 samples

a) Proteinuria and haematuria = glomerular / tubulo-interstitial disease >>>>>> investigate

b) Isolated proteinuria (without haematuria)
>>>>> Perform orthostatic test
a) Positive – orthostatic proteinuria
b) Negative – benign persistent proteinuria,
some glomerular and tubulointerstitial diseases,
reflux nephropathy, renal hypoplasia,
nephrotic syndrome.

HISTORY – preceding streptococcal infection, SLE, UTI, oedema, gross haematuria, failure to thrive,
drug ingestion, oliguria, urethral or vaginal discharge. Family history of nephritis, renal failure.

EXAMINATION- growth parameters, BP, oedema, renal masses, obstructive uropathy, signs of collagen
vascular disease, skin or throat sepsis, genital discharge.

LABORATORY INVESTIGATION OF PERSISTENT PROTEINURIA

General:
• Qualitative orthostatic test – void at bedtime. Collect first void in the morning and last void at night for
3 consecutive days and label “a.m.” and “p.m.”. Freeze and test (on return to clinic) for protein.
Trace/ negative proteinuria on recumbent (“a.m.”) urines and > 1+ on ambulant (“p.m.”) urines
= orthostatic proteinuria.
• Urine microscopy – centrifuged and uncentrifuged, MSU for culture.
• Urea, creatinine, electrolytes, albumin and total proteins (blood).

25
• Spot urine for protein /creatinine (+/- 24 hour urine protein and creatinine collection).
• Hb and Hb electrophoresis.

Specific:
For orthostatic proteinuria
• If < 12 years and proteinuria <1.0 gm/day - as for general investigations
Follow –up – yearly examinations and repeat of renal function tests and urine protein quantitation
• If >12 years old and proteinuria > 1.0 g/day – investigate as for non orthostatic proteinuria (see below)

For persistent non orthostatic proteinuria

• ASTO, ANF, C3, VDRL, Hepatitis B surface antigen
• Renal ultrasound (renal anatomy) +/- renal glucoheptonate renal scan for scarring
• MCUG if reflux nephropathy or obstruction suspected
• Renal biopsy may be indicated

INDICATIONS FOR RENAL BIOPSY IN PROTEINURIA

-Atypical nephrotic syndrome
-Failure to thrive, systemic illness
-Haematuria and proteinuria (suggesting nephritis)
-Renal failure
-Family history of chronic nephritis or renal failure
-Increasing proteinuria on follow-up.
If all tests normal and proteinuria is not nephrotic – diagnosis is Benign Persistent Proteinuria.
Follow-up as for orthostatic proteinuria

Prognosis:
Benign persistent proteinuria – excellent
Orthostatic proteinuria – 85 – 90 % of adults lose their proteinuria over 10 years of observation.

References:
1. Urinary protein excretion in healthy children. Mitenyi M. Clinical Nephrology (1979) 12; 216-221
2. Pediatrics in Review (1984) 8: 248-254
3. An office approach to hematuria and proteinuria . Ped Clin N Am (1987) 34:345-552

26
 CHAPTER 4

ACUTE GLOMERULONEPHRITIS (AGN)

Definition:
AGN is acute glomerular inflammation characterized by haematuria, proteinuria, hypertension, oliguria and
azotemia.

Aetiology:
In the local context, acute post infectious GN (most frequently post Streptococcal (PSGN)) is the most
common, followed by Hepatitis B, syphilis, typhoid, leptospirosis, HIV to name a few. Less frequent
causes include:
• Multisystem disease eg auto-immune (Systemic Lupus Erythematosus -SLE, polyarteritis nodosa),
Henoch Schonlein Purpura, Haemolytic uraemic syndrome (HUS), Wegener's granulomatosus
• Primary glomerular disease e.g. IgA nephropathy (Berger's disease), Good pasture's syndrome,
idiopathic membranoproliferative GN
• Drugs e.g. penicillamine

History:
Sore throat, skin sores, arthralgia, arthritis, skin rash, (petechial, prupuric or malar) , systemic symptoms,
preceding diarrhoea (bloody or otherwise) seizures (HUS). Urine: colour and volume; headaches, vomiting.
Previous treatment, family history of nephritis, deafness, haematuria.

Examination:
Height, weight, body surface area (m2) , oedema, skin rash, joint involvement, BP, cardiac failure,
hypertensive encephalopathy, fundoscopy.

Investigations:
Spot urine- -
• microscopy of sediment of fresh centrifuged urine for rbc, WBC, casts (record as # seen/ high power
field)
• dipstix for blood, protein, pH
• to Chem. Path for protein and creatinine (calculate urine protein/creatinine to quantitate proteinuria
Microbiology- skin and throat swabs if indicated; stool cultures especially in suspected HUS
Blood -
• Hb, Hb electrophoresis, WBC and film (ESR unhelpful), platelet count, PT, PTT, (if gross haematuria
or if HUS suspected,)
also add Fibrinogen and fibrin split products if HUS suspected
• blood urea, creatinine, electrolytes and bicarbonate, serum calcium, phosphate and albumin (note
calcium correction for hypoalbuminemia –see Chapter 1) (In PSGN blood urea/creatinine ratio is
elevated and cannot be used to determine if renal failure is intrinsic renal or pre-renal.) Estimate GFR
using Schwartz formula using Ht and serum creatinine (Chapter 1)
• Serology: - C3 (in all patients)
- ASTO, C3 - if history and examination suggest PSGN. ASTO should be repeated in 2
weeks.
- add ANF, VDRL, Hepatitis B surface antigen, Immunoglobulins if cause of nephritis
uncertain from clinical features
- add HIV if features suggestive, and HTV-1 if infective dermatitis
- (WIDAL - if indicated ). Leptospira agglutination tests (to Government Veterinary
Lab)
• Early renal biopsy if cause of AGN appears not to be Post Streptococcal- eg SLE, Hepatitis B, or if
renal failure severe or persistent (Nephrology consult)
• Late renal biopsy - failure of suspected PSGN to resolve as expected
Haematuria should be diagnosed by urine microscopy (>5rbc/hpf), and not by Labstix or the colour of the
urine

27
Importance of Complement measurement
C3 is diagnostically helpful as it is usually reduced in acute PSGN, membranoproliferative GN (MPGN),
SLE, typhoid, syphilitic and shunt nephritis, cyroglobulinaemia, bacterial endocarditis, some cases of HUS,
but is normal in most other glomerular diseases.

Treatment
1. Admission criteria: oedema, renal impairment, hyperkalemia, oliguria, hypertension, poor likelihood of
out-patient follow-up.
2. Bed rest necessary only if uncontrolled hypertension, or clinically ill
3. Penadur in therapeutic doses for Streptococcal infection (Remember dose adjustment if renal failure)
4. Diet: low sodium - 2mEq/kg/day if normotensive, 1mEq/kg/day if hypertensive; low K (1.0-
0.5mEq/kg/day), low protein 1g/kg/day (or less if uraemic), low phosphate if in renal failure. Maintain
dietary restrictions until oliguria, oedema, hypertension and azotaemia resolve.
5. Fluids; 75% of maintenance for the first 24 hours then 400ml/m2/day (insensible) + previous day's
urine output. More severe fluid overload may require stricter fluid restriction initially. If congestive
cardiac failure - fluids at 400ms/m2 only and consider dialysis (Digoxin ineffective in cardiac failure
due to fluid overload) (See also Capter 6)
6. Hyperkalemia:
(K+) 5-6mEq/l- dietary restriction and Furosemide
(K+) 6-6.5 NaHCO3 and Resonium A (Kayexalate ) - sodium sulfonic polystyrene
(K+) > 6.5 NaHCO3, glucose and insulin, dialysis
7. Blood pressure (BP) every 4 hours
8. Accurate intake and output, daily weight
9. Urinalysis daily - first morning urine, urine microscopy of centrifuged urine at least once per week and
on discharge
10. Blood urea, creatinine, bicarbonate, electrolytes (U+E's) daily until oliguria ceases, renal function is
stable and electrolyte imbalance has resolved, the at least weekly.
The results of U+E's in all renal patients must be reviewed the same day that the sample is collected
11. Note indications for peritoneal dialysis (Chapter 11)
12. For hypertension: (see also Chapter 13)
- If intermittent and mild - Hydrallazine 0.2mg/kg IM q4h prn for diastolics > 95th % for age
and height
- Furosemide IV /po (1mg/kg if normal renal function; 2mg/kg (or more) if renal failure)
may be added
- Mild/moderate - Furosemide, Hydrallazine +/- B blocker (if not asthmatic or in heart
failure), Ca channel blocker eg Nifedipine, ACE inhibitor eg. Captopril
- Severe - (see Hypertensive crises) - Furosemide IV / Diazoxide IV / sublingual Nifedipine
/ Minoxidil po, or titrated IV Hydrallazine, Na nitroprusside IV infusion
13. IV Furosemide 1-2 mg/kg/day as as single dose (maximum single dose 10mg/kg) - on admission if
oliguria is marked
14. Discharge when oedema has resolved, hypertension has resolved or is controlled, and azotaemia is
resolving.
15. Treat underlying cause of AGN if evident (eg SLE)

Follow-up of AGN:
If uncomplicated PSGN with normal couse of resolution, follow for at least 2 years or until urinary
abnormalities resolve. (Local data on PSGN in childhood is awaiting analysis). Longer-term follow-up
would be required for: nephrotic proteinuria or nephrotic syndrome, severe renal failure, atypical course for
PSGN (see below)
On each visit - BP, height, weight, and urinalysis for blood and protein, centrifuged urine microscopy if
possible. Always check that results are normal and refer to POPD renal if they are not.
At 6 weeks post AGN in addition: repeat C3 (should be normal), Hb, urea, creatinine, electrolytes,
bicarbonate, albumin, spot urine protein/creatinine to quantitate proteinuria, estimate GFR (Schwartz
formula – Chapter 1)
At 6 months post and 1 year post AGN and yearly thereafter - investigate as for 6 weeks post but omit C3.

28
 NORMAL COURSE IN ACUTE PSGN

ABNORMALITY MAXIMUM DURATION

Oliguria 2 weeks
Gross haematuria 4 weeks
Azotaemia 4 weeks
Hypertension 4 weeks
Hypocomplementemia 6 weeks
Haematuria with proteinuria 6 months
Isolated microhaematuria or isolated proteinuria (low grade) years

Consider renal biopsy / nephrology consultation in patients with suspected acute PSGN who:
1. Fail to respond as above
2. Have nephrotic syndrome
3. Have severe renal failure (estimated GFR < 50% of normal for age)
4. Have rapidly progressive course
5.
RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS

Though it is somewhat controversial, some authors recommend, that all children with SLE should have a
renal biopsy as renal pathology may be present even in the absence of clinical renal involvement. Repeat
biopsy may be needed if the clinical presentation changes, or to monitor response to therapy

Histological classification:
Class 1 - normal histology - asymptomatic - no treatment required
Class II - mesangial proliferation- mild proteinuria and microscopic haematuria, usually normal glomerular
function- no specific treatment- careful follow-up as progression is possible
Class III - focal segmental GN
• < 20% glomeruli involved - < 5% risk of progression to renal failure within 5 years
• > 40% glomeruli involved - more severe - active urine sediment, nephrotic syndrome,
hypertension, +/- moderate renal insufficiency - similar to DPGN (Class IV GN) -same
treatment as Class IV
Class IV - diffuse proliferative GN - severe - haematuria with casts, nephrotic syndrome, hypertension,
moderate to severe renal insufficiency -high risk for end stage renal disease if not treated aggressively
- IV pulse methyl prednisolone 30mg/kg (maximum I gm) daily for 3 doses, followed by IV
Cyclophosphamide monthly for 6 months with daily oral prednisone weaned over several
months. (Nephrology consultation required)
Class V -pure membranous - mild proteinuria, normal renal function,- good prognosis- 5 year survival 85%
- no specific treatment - (?treatment if nephrotic)
-membranous with proliferation - moderate proteinuria +/- haematuria +/- nephrotic syndrome,
moderate renal faiure, hypertension - treatment with IV pulse methyl prednisolone / Chlorambucil / and
oral steroids (Nephrology consultation required)
Class VI - chronic sclerosing GN - end stage renal failure - unlikely to be responsive to treatment

HAEMOLYTIC URAEMIC SYNDROME (HUS)

Definition:
Triad of acute renal failure, microangiopathic haemolytic anaemia (fragmented rbc) and thrombocytopenia.
Thrombocytopenia is not invariable and thrombocytosis may be noted if diagnosis is made late. In North
America, most cases are of classical HUS with the prodrome of bloody diarrhoea (D+ HUS), and are
associated with verotoxin producing E coli (Stx HUS) - Shiga toxin associated HUS). In HUS, diarrhoea
may not be bloody and may even be absent, and it may follow a respiratory prodrome. HUS may occur
with UTI secondary to Stx producing E coli 0103:H2, and with other infections such as Strep pneumonia,

29
Typhoid fever, gram negative septicemia, HIV and HTLV-1. In Jamaica, our cases appear to be triggered
by systemic infections, have severe CNS involvement and guarded outcome, but data are preliminary and
our cases are few. Thrombotic thrombocytopenic purpura (TTP) - another form of thrombotic
microangiopathy (TMA) is similar to HUS, but differs primarily in that it is mainly a disease of adults, and
whereas HUS affects the kidneys predominantly, TTP tends to have more multisystem involvement. The
distinctions are not always clear-cut. Differentials include Viral Haemorrhagic Fevers, Leptospirosis and
DIC.

History:
• HUS should be suspected when a patient with diarrhoea develops progressive oliguria despite
correction of dehydration, sudden pallor, mild jaundice (secondary to haemolysis) and petechiae (from
thrombocytopenia).
• Diarrhoea (type), haematuria, oedema, cough, myalgia, fever, jaundice, abdominal pain, vomiting,
oliguria, anuria, conjunctivitis, seizures, decreased conscious level, bleeding. Enquire about water
source? boiled, milk source ? pasteurized, presence of mosquitoes (Dengue) and rats ( Leptospirosis) ,
other affected individuals
• Past history - previous illnesses, renal disease, sickle cell disease, seizures and drugs. Family history
of renal disease
• Examination: as for acute glomerulonephritis. Note jaundice and eye signs (corneal clouding-
observed in our cases)

Investigations at UHWI

1. Haematology:
• Hb electrophoresis, Hb, WBC, differential, platelet count, reticulocyte count and film - for
fragmented and burr cells and reticulocytosis
• PT, PTT ,G6PD screen, fibrinogen and fibrin degradation products (special tubes from
Haematology)
• Repeat haematology including film daily or alternate days ,and coagulation screen as indicated
• Direct Coomb's test, cross match and reserve 10cc/kg packed cells and 20cc/kg FFP if bleeding or
ill looking
• Haematology consult
2. Chem Path:
• blood urea, creatinine, electrolytes, bicarbonate, albumin, calcium, phosphate ,alkaline
phosphatase, SGOT.,GGT, LDH, HBD, glucose, amylase (watch for hepatitis and pancreatitis)
• spot urine - protein, creatinine, phosphate ( calculate degree of proteinuria and tubular
reabsorption of phosphate), Na, K
• urine microscopy (centrifuged)
• Estimate GFR using Schwartz formula
• daily urinalysis for protein and blood

3. Serology / virology / microbiology;

• C3, ANF, VDRL (+ Hepatitis B surface antigen if jaundiced
• Leptospira agglutination test - (clotted sample sent to Government Veterinary Laboratory by
ambulance, WIDAL and clot culture ( if diarrhoeal prodrome), Immunoglobulins, HIV ( if infections
severe)
• Acute and convalescent serum - 10 days apart (7.5 -5cc) to Virology, labeled Haemolytic Uraemic
Syndrome. Give details of symptoms on the form
• Stool (no preservative) or rectal swab for viral culture
• Stool - culture and sensitivity (C&S), and ova and parasites
• Swabs of infected lesions for C&S, CSF ( if LP done) , MSU for viral and bacterial cultures, blood C&
S when indicated
• ALL VIRAL SWAB CULTURES ARE TO BE SENT IN TRYPTOSE PHOSPHATE BROTH-
labeled Haemolytic Uraemic Syndrome

30
NOTE:
• For patients with CNS involvement - Cranial CT scan, EEG, Neurology consult
• Nephrology consult- all cases, renal ultrasound (+/- Renal biopsy)
• Ophthalmology consult within 2 hours if abnormal eye examination eg cloudy cornea
• Investigate symptomatic contacts as per index case (1-3 above)
• All deaths should have Post Mortem - (contact Nephropathologist) -special attention to kidneys , brain,
lungs, liver, pancreas, heart, GI tract and any skin lesions

Initial treatment protocol

1. Catheterize all anuric/oliguric patients to accurately ascertain urine output. Accurate intake and output
measurements
2. Correct volume depletion of present by boluses of saline or Hartmanns's 20cc/kg over 1-2 hours or less
depending on degree of dehydration. Repeat if necessary.
3. If oliguria /anuria / renal failure persist despite (2) try Furosemide 2-4mg/kg IV push.
4. If still oliguria despite (2) and (3) or if fluid overloaded, uraemic, hyperkalemic, acidotic,
hyponatremic, hypertensive - peritoneal dialysis is indicated.
5. IV-D10W with 2mEq NaHC03 /kg/day at 400ml/m2 fluid /24 hours -till acidosis corrected. Increase
volume of D10 IV or p.o fluids when dialysis started and fluid overload corrected. Replace all losses -
stool, nasogastric drainage q4 h and urine q 1-4 hourly depending on volume
6. If phosphate elevated- treat with phosphate binders
• Preferably Calcium carbonate 20-220mg/kg/day (Tums ) 1 tab = 500mg Ca CO3 in 1-3 divided
doses (with meals if eating)
• or Aludrox 5-10 mls q 12 -6 hourly (less ideal)
7. If symptomatically hypocalcemic (serum calcium <1.9mmol/l) despite correction for
hypoalbuminaemia, start calcium infusion of 10% calcium gluconate: 0.2mEq/kg/hr of Ca2+. Repeat
serum calcium q4 h during infusion and adjust rate q4 h to keep serum Calcium 2.25mmol/l -
2.75mmol/l. (Check serum phosphate daily, serum albumin alternate days). 1 cc of 10% calcium
gluconate -0.45mEq Ca2+ (See Chapter 7 for dilution of infusion)
8. GI bleed - ice cold saline lavage till clear - NGT on free drainage - aspirate q4 h and replace losses
with D10/ N saline. Calcium carbonate (or other antacid) 5-10 cc q2h via NGT - clamp 1/2 hour after
drug administered. - Dialysis will be required.
9. Seizures (hypertension, hypocalcemia, hyponatremia, uraemia, CNS infarct or bleed)
• Abort seizure with conventional anticonvulsants
• Treat acute hypertension (Hydrallazine titrated IV, IV push Diazoxide, sublingual Nifedipine, oral
Minoxidil or (in ICU) Na Nitroprusside) and then maintenance antihypertensives (see Chapter 13)
• Correct metabolic disorder - Dialysis may be necessary
• If seizures refractory to maximum doses of conventional anticonvulsants, may need to add
paraldehyde infusion -5.0 ml (1gm/ml) in 95cc of D5 0.2Ns at 0.5 -2cc/kg/.hr depending on
response
• Neurology consult may be necessary
10. Packed cells 5cc/kg slowly e.g .(over 4 - 6 hours) if Hb < 6g/l and active haemolysis or bleeding. More
rapid infusion if shock or active bleeding. Risk of worsening hypertension and seizures during or after
transfusion if blood administered too quickly.
11. Platelets 0.2units /kg UV if platelet count <20,000/ml, or if active bleeding (Contact Haematology)
12. FFP if abnormal PT/PTT and bleeding. Plasma infusions are not recommended in D+HUS
13. In hypotensive, volume overloaded , oliguric patients:
• CVP line (contact surgeons early)
• IV dopamine 4-10µg/kg/min in ICU adjusted to maintain normal BP
• Dopamine dose dilution : (Dopamine dose (mg) for dilution = 6mg/kg )
• diluted to 100cc with N saline - run at 1cc/hr = 1µg/kg/min Dopamine
14. Watch for pancreatitis and hepatitis complicating HUS

31
Follow-up
1. Renal / liver : monitor blood urea, creatinine, electrolytes, albumin, bicarbonate, calcium, phosphate,
liver function tests every 3-6 months with Hb, WBC platelet count and reticulocytes. repeat C3 if
initially low. Urine: dipstix for blood and protein with microscopy for cells, Blood pressure and
growth parameters each visit.
2. Neurological- follow-up if CNS involvement, at least once to twice yearly in Neurology clinic. If
seizures were metabolic and no structural CNS damage present, anticonvulsants may be weaned off
before discharge once the underlying problem has been corrected.

References:
1. Acute glomerulonephritis - a clinical review. Medical Clinics of North America (1984) 68:259-279
2. Acute Glomerulonephritis -diagnosis and treatment: Pediatr Clin N America (1982) 29: 857 -873
3. Acute glomerulonephritis and crescentic glomerulonephritis Chapter 41. Pediatric Nephrology (1999)
4th Edition. Barratt, Avner and Harmon Eds. pages 669-689
4. Systemic lupus erythematosus Chapter 49 Pediatric Nephrology (1999) 4th Edition Barratt, Avner and
Harmon Eds -pages 793-810
5. Treatment of lupus nephritis in children - Pediatric Nephrology (2000) 14: 158-166
6. Hemolytic uremic syndromes Chapter 50 Pediatric Nephrology (1999) 4th Edition Barratt, Avner and
Harmon Eds - pages 811-834

32
 CHAPTER 5

NEPHROTIC SYNDROME (NS)

Definition:
1. Massive proteinuria
• > 0.05mg/kg/day or
• > 40mg/m2 /hr on a 12 -24 hour collection or ideally an overnight sample
• random urine protein/creatinine > 2 (mg/mg)
• overnight urine protein/creatinine > 1.8 (mg/kg) _ Clin Neph (1988) 30: 225-229
• persistently > 3+ proteinuria on qualitative assay on early morning urine sample
2. Hypoalbuminaemia (< 25g/l)
3. Oedema
4. +/- hypercholesterolemia or hypertriglyceridemia

Aetiology:
Minimal change nephrotic syndrome is quoted in world literature as the commonest cause of childhood NS,
but our local data (1984 - 1996) suggest that mesangial proliferative GN may be as almost as common.
Primary nephrotic syndrome is more common than secondary. Secondary causes in our series include: post
infectious - post Streptococcal GN, Hepatitis B, syphilis, HIV and HTLV-1, auto-immune-SLE, Sickle
haemoglobinopathy, and Wilms tumour

Other definitions:
Relapse: Proteinuria > 2+ on dipstix or sulfosalicylic acid (SSA) for 5 consecutive days, or proteinuria >
2+ on any day with oedema (cloudy urine on SSA testing)
Remission: Trace/ negative proteinuria for 5 consecutive days (clear urine on SSA testing)
Frequent relapses: > 2 relapses within 6 months
Steroid resistance: failure to achieve remission after a 28-day course of daily Prednisone

History:
• Sore throat, (preceding or current), gross haematuria, symptoms of collagen vascular disease, sickle
cell anaemia, skin lesions - eg infective dermatitis (HTLV-1), skin sores (PSGN), purpura (Henoch
Schonlein Purpura) or HUS or collagen vascular
• Previous treatment and response
• Family history of renal disease, sickle cell anaemia, maternal syphilis

Examination:
Growth parameters, BP, oedema, signs of secondary nephrotic syndrome

Investigations:
• CBC, Hb electrophoresis, electrolytes, bicarbonate, urea, creatinine, serum albumin, calcium and
phosphate.
• For every 10g/l that albumin is below normal, the true serum calcium is 0.2mmol/l higher than
the measured value
• cholesterol and triglycerides not essential for diagnosis - if done should be a fasting sample . ESR is
unhelpful as it is invariably elevated regardless of the cause of nephrotic syndrome
• Serology - ASTO, ANF, VDRL, C3, Hepatitis B surface antigen. TORCH in congenital nephrotic
syndrome. HTLV-1 antibody (if infective dermatitis), HIV antibody (if suggestive history and
examination)
• Microbiology - swab skin and throat if lesions present, ascitic fluid tap for gram stain and culture if
peritonitis suspected. Other bacterial cultures if indicated.
• Urine tests:

33
 • dipstix for blood, protein and pH. Remember that alkaline UpH will give a false positive test for
protein using the dipstix. In such a case use the sulfosalicylic acid (SSA) test for urine protein.
(See Assessment of Renal Function)
• spot urine for protein /creatinine (+/- 24 hour urine for protein and creatinine - 24 hour urine
quantitation is no longer absolutely necessary )
• urine microscopy (centrifuged) for rbc, wbc and casts
• +/- Renal biopsy

Indications for renal biopsy prior to steroid therapy: (i.e. features atypical for minimal change
nephrotic syndrome (MCNS)
1. age <1 year > 12 years (relative indication in the older child)
2. history suggestive of PSGN, auto-immune disease or other secondary nephropathy
3. persistent hypertension
4. gross haematuria (microhaematuria may occur in 20% of patients with MCNS)
5. renal failure not attributable to hypovolemia
6. positive serology, sickle haemoglobinopathy
7. hypocomplementemia is absent in MCNS and is seen in membranoproliferative GN (MPGN),
crescentic nephritis, PSGN, SLE, Hepatitis B infection, shunt nephritis, infective endocarditis and
some other post infectious causes
8. anaemia Hb<10g/l (when not due to nutritional deficiency) suggests MPGN (Membranoproliferative
GN), sickle Hbinopathy ,chronic renal failure

CLINICAL DIFFERENTIATION OF COMMON TYPES OF CHILDHOOD NS - by features at

initial presentation

HISTOLOGICAL MCNS MEMBRANOUS MPGN CONGENITAL

GROUP FSGS* GN CRESCENTIC NS
Mes prolif GN** PSGN (DPGN)
usually signs of
PRESENTATION Benign benign but older fulminant underlying disease
eg syphilis
Age 1-6 years usually > 6 years any age 0-12 months
Hypertension - - + -
Gross haematuria - - + -
Renal failure - - + +/-
Anaemia - - + +/-
Positive serology - +/- + + usually VDRL

Reduced C3 - +/- + +/-

*FSGS (focal segmental glomerulosclerosis) -more likely to be hypertensive at onset - **Mes prolif GN
(mesangial proliferative glomerulonephritis)- more likely to have microscopic haematuria and mild
hypertension at onset. MPGN (membranoproliferative glomerulonephritis)- PSGN (post streptococcal
glomerulonephritis) DPGN (diffuse proliferative GN- usually post infectious)

Treatment: SPECIFIC
• Treatment with Prednisone at presentation is indicated only in those children with clinical features
suggestive of MCNS.
• All other children should be referred to a paediatric nephrologist for renal biopsy.
• Standard MCNS protocol would under-treat MPGN, and crescentic GN, putting the patient at risk for
chronic renal failure, and give unnecessary treatment to spontaneously resolving post infectious
nephritides
• Nephrotic syndrome secondary to other nephritides requires specific regimes and has variable
prognoses. Nephrology consult needed.

34
Treatment in MCNS, Mes prolif GN, FSGS:
To induce first remission: Prednisone 2 mg/kg/day (maximum 80 mg/day) - (alternatively 60mg/m2 /day)
in 3 divided doses for 28 days then
Maintain remission on first and subsequent relapses:
Prednisone 2mg/kg as a single dose on alternate mornings for 28 days then taper and discontinue over 2-3
months
To induce remission in subsequent relapses: Prednisone 2mg/kg/day (maximum 80mg/day) in divided
doses until remission occurs or for a maximum of 28 days

For steroid resistance, renal biopsy is needed. Renal biopsy is no longer indicated prior to further
therapy, for children who retain features of MCNS but have frequent relapses.

Frequent relapsing NS / steroid dependence / steroid resistant MCNS, FSGS, Mes prolif GN

1. Reduce Prednisone slowly and maintain on Prednisone / Prednisolone 0.1-0.5mg/kg alternate day for
up to 12 months
2. Relapse on Prednisone >0.5mg/kg alternate day and steroid side effects or relapse on Prednisone
>1mg/kg alternate day :
• Cyclophosphamide 3 mg/kg/day as a single daily morning dose for 8 weeks, or 2-2.5mg/kg/day
for 12 weeks (maximum cumulative dose should not exceed 250mg/kg to avoid oligospermia.
Azospermia occurs at 500mg/kg). Prednisone at 2mg/kg/day as a single alternate day dose is given
during the full course of Cyclophosphamide then slowly tapered and discontinued.
• liberal fluids and frequent bladder emptying to minimized risk of haemorrhagic cystitis
• risk of sterility after prolonged courses of > 6 months
• monitor CBC on alternate days for the first week then weekly for the first month, then every
2-3 weeks.
• if WBC <5 x 109/l but >4 X 10 9 /l , reduce dose by 10%
• if WBC <4 x 109/l, hold Cyclophosphamide and restart at 10% lower dose when WBC >5 x
109/l
• Cyclophosphamide tablet is 50mg. If patient requires a lower dose the pharmacy makes up a
solution from the IV preparation to be given orally. It is an unstable preparation and has to be
re-made every 2 weeks, so patient will have to make 2 weekly visits to have prescription
refilled.
• Discontinue Cyclophosphamide if : a) patient is exposed to or contracts rubeola or varicella b)
develops haemorrhagic cystitis
• Side effects - haematological, haemorrhagic cystitis, transient mild alopecia, risk or sterility
and secondary malignancy
• Clorambucil (if Cyclophosphamide unavailable) 0.1 -0.2 mg/kg /day as a single morning dose
for 8-12 weeks with a similar Prednisone regime as for Cyclophosphamide.
• side effects - seizures, alopecia, haematuria and risk of infection, rashes . Cumulative dose
should not exceed 10mg/kg. Azospermia occurs at >18mg/kg cumulative dose.

Frequently relapsing / steroid dependent NS despite alkylating agents- used after remission induced by
Prednisone.
1. Levamisole (Ketrax) 2.5mg/kg as a single dose on alternate mornings for 4-12 months, with
Prednisone on alternate mornings as a single dose to be tapered slowly. Side effects - leukopenia,
allergic rashes,. Monitor CBC as for Cyclophosphamide and adjust dose similarly. Discontinue if rash
develops
2. Cyclosporin (expensive) -5.0 mg/kg/day (or 100-150mg/m2/day for 1 year with alternate day
prednisone tapered slowly. Need to monitor renal function and Cyclosporin levels. Risk of
nephrotoxicity.

Other treatment protocols for steroid resistant nephrotic syndrome - usually Steroid resistant FSGS
(Nephrology consult required)
• Pulse methyl prednisolone (PMP)- short or long protocol (Nephrology consultation requried0

35
• Several other modalities have been tried- including PMP with oral Prednisone and Cyclosporin/
plasma exchange and immunoadsorption / IV Vincristine pulses / IV pulse Cyclophosphamide with
oral prednisone

Nephrotic syndrome unresponsive to all therapeutic modalities - ACE inhibitors eg Captopril, Enalapril, for
protein sparing effect (S/E hyperkalemia, hyponatremia), diuretics for oedema control, Indomethacin
• Enalalpril 0.2 - 0.8 mg/kg/day o.d. for prolonged periods (not for neonatal use)
• Captopril 0.75mg/kg/ day (t.i.d) - increased by 1mg/kg each week if no response, to a maximum of
5mg/kg/day- maximum response in 6 weeks
• Captopril/ Indomethacin 1mg/kg/day increased by 1mg/kg each week till response or maximun of
5mg/kg/day - risk of renal impairment
• Vitamin E 200IU bid - said to reduce proteinuria in steroid resistant FSGS

Treatment - general
• NB - In patients with nephrotic syndrome associated with renal failure and volume overload, the
management of the acute renal failure takes priority, and the patient is managed as for AGN with fluid
restriction.
• DO NOT GIVE COLLOID TO PATIENTS (EVEN IF NEPHROTIC) IF THERE IS CLINICAL
INTRAVASCULAR VOLUME OVERLOAD

Treatment of patients with NS and presentation as per MCNS

1. Diet - Normal protein - 2mEq/kg/day while on daily steroids or oedematous
2. Fluids- maintenance for estimated dry weight. Fluid restriction in MCNS type nephrotic syndrome
will result in further intravascular volume depletion and pre-renal failure
3. Accurate intake and output and daily weight
4. Daily testing of first morning urine for protein (avoids detection of orthostatic proteinuria)
5. Culture and treat suspected systemic infection with antibiotics which cover both gram negative and
gram positive organisms eg Amoxil and an Aminoglycoside
• Peritonitis is usually primary and due to Pneumococcus. A peritoneal tap will isolate the organism
. Finding several GNB on a peritoneal tap suggests a perforated viscus and a surgical abdomen. A
single gram positive organism is likely to be due to the NS and surgical consult is not needed as
this will resolve with medical treatment
• Pneumonia is often pneumococcal
6. Oedema -
• mild - no treatment required. Diuresis in 8-10 days of Prednisone if steroid sensitive
• moderate - with normal renal function - Rx Spironolactone 3-5 mg/kg/day in 3 divided doses.
Increase from lower dose every 5 days if inadequate response. Monitor electrolytes for
hyponatremia and hyperkalemia. Combination with a thiazide Hydrochlorothiazide 1-2mg/kg
/day (od) or Bendrofluazide 0.1 - 0.2mg/kg/day (od) is often helpful
• severe - see albumin and Furosemide

Furosemide should not be given without first giving colloid (albumin or plasma) in children with
MCNS type NS. Potent diuretics and severe fluid restriction may precipitate pre- renal failure.
Indications for colloid / and Furosemide
Nephrotic patients with anasarca, pre-renal failure, massive ascites or pleural effusions causing respiratory
distress, abdominal pain secondary to mesenteric ischaemia should ideally have 25% salt poor albumin
1g/kg IV over 2 - 4 hours followed by Furosemide 1 mg/kg IV after 2 hours of the infusion. If this is not
available, Fresh frozen plasma (FFP) (20cc/kg) over 4-6 hours with Furosemide 1mg/kg halfway through.
Watch for hypertension (treat with antihypertensives and reduce infusion rate) and cardiac failure (stop
infusion and give diuretic).

Follow-up
• Patients should be educated about nephrotic syndrome and taught how to test the first morning urine
daily and record in a notebook. Labstix are expensive. 3% Sulfosalicylic acid (SSA) is available from

36
 Chemical Pathology in stock bottles, which are kept on the ward. The bottles are to be kept filled and
'topped up before each renal clinic so patients may be supplied with the fluid. Usually 300cc is
adequate for about 2 months. Relapse and remission and the treatment of each, are explained. The
Prednisone dose for relapse is written in their book.The need for medical attention if relapse, fever or
exposure to measles or varicella occurs is emphasized.
• NO LIVE VIRUS VACCINES SHOULD BE GIVEN TILL THE PATIENT HAS BEEN IN
REMISSION AND OFF PREDNISONE FOR AT LEAST 3 MONTHS
• Patient instructions for 3% SSA test: patient is supplied with 2 plain tubes as well as SSA.
• The first morning urine is tested.
• A "finger joint" height of urine is poured into the test tube and an equal portion of SSA added.
• If the liquid is clear like water or coconut water and print can be read through it - the test is
recorded as "CLEAR"
• If the liquid is cloudy and print cannot be read through it - the test is recorded as "CLOUDY'
• Relapse is "cloudy" urine for 5 days consecutively or any day with swelling (kidney is sick)- start
Prednisone in 3 divided doses and come to hospital to be checked
• Remission is "clear" urine for 5 days consecutively (kidney is getting better) - take all the day's
Prednisone as a single dose on alternate mornings

Complications of chronic steroid resistant NS

• Hypocalcemia - may need Vit D therapy
• Hypothyroidism - may need Thyroid supplements
• Anaemia - check for iron deficiency
• Risk of infection - Penicillin prophylaxis (Pen V-daily or Penadur- monthly) to be considered for
children with a history of Pneumococcal sepsis with relapses. ? Role of Pneumococcal vaccine in our
population of childhood nephrotics
• Hyperlipedemia - potential risk of accelerated atherosclerosis: treatment uncertain? Bile acid
sequestrants (Cholestyramine, Sitoserol) / Fibrates (Benzafibrate, Gemfibrozil). The safety of statins in
children has not been established.
• risk of CRF

References:
1. Consensus statement on management and audit potential for steroid responsive nephrotic syndrome
Arch Dis Child (1994) 70: 151 -157
2. Steroid-responsive nephrotic syndrome Chapter 45, 731-747 Pediatric Nephrology 1999 4th Edition.
Barratt, Avner and Harmon Editors.
3. Steroid -resistant nephrotic syndrome Chapter 46, 749-777 Pediatric Nephrology 1999- 4th Edition .
Barratt, Avner and Harmon Editors
4. Management of the nephrotic syndrome in children. Pediatr Clin N America 23: 735-750
5. Nephrotic syndrome in childhood Pediatr Clin N America (1982) 29; 975-894
6. Should hyperlipidemia in children with nephrotic syndrome be treated? Pediatr Nephrol (1999) 13: 77-
84
7. Enalalpril and prednisone in children with nephrotic range proteinuria . Pediatr Nephrol (2000) 14:
1088-1091
8. For urine protein/creatinine ration: J Peds (1990) 116: 243-247
9. For treatment of hyperlipidemia : Pediatrics (1992) 89:495-501, 138-142, Suppl 525-584

37
 CHAPTER 6

DISORDERS OF ELECTROLYTE AND WATER BALANCE

Sodium
Sodium is the major extracellular cation. Changes in sodium balance reflect changes in the volume of
extracellular fluid (ECF). Aberrations in water balance or ECF osmolality reflect changes in the balance
between total body sodium and total body water.

Sodium balance – Factors controlling sodium loss –

Aldosterone dependent.
Non aldosterone dependent
• Na excretion increased by – high GFR, high renal blood flow (RBF), haemodilution, atrial
natriuretic peptide (ANP), Dopamine, nitric oxide (NO), ADH, thyroxine, calcitonin,
glucagon, prostacyclin, oestrogen and progesterone.
• Na excretion reduced by- very low GFR, low RBF, haemoconcentration, nor adrenaline,
prostaglandin inhibition.
Control of water balance
1. Thirst – thirst centre in the hypothalamus –responds to changes in plasma osomolality. Increases in
blood osmolality resulting in thirst and increased water intake
2. Increased Posm causes secretion of ADH (antidiuretic hormone) from the osmoreceptors in the
supraoptic and paraventricular nuclei of the hypothalamus. ADH acts? via aquaporins (water channels
in the collecting ducts) to increase the permeability of the distal renal tubular cells and increase water
reabsorption along an osmotic gradient resulting in a concentrated urine of high osmolality.
3. Non ADH dependent: When there is a high solute load in the glomerular filtrate, (eg glucose,
mannitol), the substrate is not fully reabsorbed from the PCT and loop of Henle resulting in the
inhibition of water and Na reabsorption in the PCT, a larger than normal volume in the DCT and
diuresis.

Maintenance requirements (Table 1)

Fluid (infants and children) 100ml/kg for first 10 kg body weight

50ml/kg for second 10kg
20ml/kg after 20kg

Neonate 120-150ml/kg/day by day 4

Premature neonate May exceed 200ml/kg/day (higher in premature

neonates)

Sodium 2-3mEq/kg/day (higher in premature neonates)

Potassium 2-3mEq/kg/day

Ca 2+ 2mEq/kg/day

Fluid requirements in fever:

• For every oC rinse in temperature above 370C, fluid requirements increase by 10% of calculated
daily maintenance or
• 10 mls/kg/day
• For every 0F rise in temperature above 99oF, water loss increases by 7mls/kg/day

38
DEHYDRATION
Dehydration reflects a reduction in total body water and may be classified by degree (mild, moderate,
severe) or in relation to serum sodium values (iso- hypo- and hypernatremic). The commonest cause of
dehydration is gastroenteritis. Mild to moderate dehydration may be corrected orally.

Assessment of Degree of Dehydration – (Table 2)

Degree % Wt % Wt loss Fluid deficit Fluid Clinical
loss Child (ml/kg) deficit
Infant Infant (ml/kg)
Child
Mild 5% 3% 50 30 Reduced secretions (tears, sweat, urine
output)
Moderate 10% 6% 100 60 Reduced tissue turgor – sunken
fontanelles and eyes, and reduced skin
turgor (abdomen), further oliguria and
tachycardia
Severe 15% 9% 15 90 Shock, reduced conscious level, fever,
severe oliguria

Types of Dehydration:
• Isonatremic (isotonic) – serum sodium normal
• Hyponatremic (hypotonic ) – Na <130mmol/l – earlier ECF and plasma volume depletion
• Hypernatremic (hypertonic) – Na >150mmol/l – plasma and ECF volume preserved longer

Etiology of Dehydration
May be secondary to decreased intake or increased losses from kidney, GI tract, lungs or skin. If USG is
>1.012 and U Na is <5mmol/l dehydration is non renal in aetiology.
If USG < 1.010 and UNa 10 – 20mmol/l, dehydration is caused by renal fluid loss e.g. diabetes insipidus.

History : Assess volume and type of intake and output, duration of losses, fever and treatment given.
Examination: Growth parameters, tempreature, BP, pulse, hydration status, level of awareness, associated
sepsis, acidotic breathing.

Investigations
General: Hb, WBC, differential, electrolytes, bicarbonate, urea, and creatinine. If dehydration is moderate
to severe, add calcium, glucose and albumin. Cross match for plasma if very severe. Spot urine for specific
gravity and urine Na.
Specific: Septic work-up if indicated, include urine cultures, stool cultures and parasitology where
indicated.

Treatment
1. Resuscitation: correct shock if present – 20 cc/kg IV bolus as rapidly as possible using isotonic fluid
5% dextrose in normal saline, Hartmanns, fresh frozen plasma (FFP). FFP preferred if patient is
malnourished. Repeat bolus as often as is necessary to obtain satisfactory blood pressure and pulse
rate. Whole blood preferred if anaemic and in shock.
2. Add maintenance fluid (Table 10 to fluid deficit (Table 2)
3. Estimate ongoing losses
4. Subtract the volume used in resuscitation (1)from the maintenance +deficit volume (2)
5. In hypo or isonatremic dehydration
• Give half of the remaining maintenance + deficit volume (2)-(1) over the first 8 hours and the
remainder over the next 16 hours
• Estimate and replace ongoing losses q4h with fluid of appropriate concentration
• Add KCl 10mEq/500ml of IV fluid once urine has been passed. May need more or less K
depending on renal function, serum K and ongoing losses.

39
 Milder degrees of dehydration may be corrected orally using Oral Rehydration Fluid (ORF), but applying
the same principles for fluid management
6. If breathing is acidotic and serum bicarbonate unavailable, give Na bicarbonate 2mEq/kg IV: 1
mEq/kg diluted to 50% with water for injection and given over 15-30 minutes and the remainder in IV
fluids over the next 2-3 hours. Reassess acid base status when serum bicarbonate available (additional
bicarbonate may be necessary).
7. If serum bicarbonate <12mmol/l- determine bicarbonate deficit and supply in IV fluids over 2-3 hours.
Correct bicarbonate to about 15mmol/l
Bicarbonate deficit (mEq or mmol) = (Desired – Initial Bicarbonate X 0 .6* X body wt (kg)

8. Correction of hyponatremia
Na deficit (mEq) = (Na desired – Na actual) x 0.6* x body wt. (kg)
*(in infants 0.75 should be used instead of 0.6)

Fluids given should provide sufficient sodium to

• Replace deficit Na
• Supply maintenance Na
• Supply ongoing Na losses

Profound symptomatic hyponatremia (Na < 120mEq/l) with seizures or coma requires rapid correction
to 130mEq/l with hypertonic saline (6% NaCl or if not available 8.4% NaHC03).
• Serum Na should not rise by more than 10mEq/l/hour during correction to avoid CNS
demyelination.
• 6mEq/kg of NaCl /kg increases serum Na by 10mEq/l
9. Monitoring : careful monitoinr of response is crucial – (BP, HR, hydration, urine output, losses,
weight, laboratory data) to determine adequacy of treatment. Fluid calculations are only guidelines
and must be adjusted according to patient response.

Sodium composition of various preparations (Table 3)

1gm salt 20mEq Na+
1gm sodium 40mEq Na+
4.3% dextrose in 0.18 N 31mEq Na+/l
saline
D5 / 0.45 N saline 77mEq Na+/l
D5 / N saline 154mEq Na+/l
6% Na Cl 1mEq Na+/ml
8.4% Na bicarbonate 1mEq Na+/ml

Approximate electrolyte composition of gastrointestinal fluids (mEq/l) (Table 4)

H+ Na+ K+ Cl- HCO3 -

Gastric 80 40 20 150 0
Small intestinal 0 130 20 120 30
Pancreatic 0 135 15 100 50
Diarrhoea 0 40-70 40 40 40

Hyponatremia (serum sodium <130mmol/l)

Classification:
• False / pseudo hyponatremia – in hyperlipidemia, secondary to mannitol infusion and secondary to
hyperglycemia. For correction of serum Na for hyperglycemia see “Assessment of Renal Function –
Chapter 1. Hyperglycemia - associated hyponatremia will correct when hyperglycemia ceases and is
asymptomatic.

40
• True hyponatremia

History: - gastroenteritis, polyuria, diuretics, excessive sweating, liver or renal disease, ambiguous
genitalia, hypothyroidism and drug ingestion. The severity of the symptoms (changes in sensorium)
depends on the rate at which the sodium has fallen. Signs and symptoms are more likely when the fall is
rapid and are most likely due to cellular swelling and cerebral oedema. Seizure and coma are most likely to
occur when serum Na falls below 120mmol/l. Elevation of serum Na to approximately 130mmol/l is
usually sufficient to correct the acute symptoms of hyponatremia. The treatment of hyponatremia depends
on the cause.

Examination – hydration status, signs of endocrine, or renal disease. Blood pressure, oedema, cardiac
failure. Check growth parameters and nutritional status.

General investigations:
• Electrolytes, bicarbonate, urea, creatinine, glucose, Hb.
• Spot urine – Na before any diuretic is given, urine specific gravity and osmolality, urine microscopy
of centrifuged urine (rbc and casts) and urinalysis for blood and protein

Evaluation of hyponatremia

Clinical examination

Hydration normal or slightly increased

Dehydration No oedema Oedema

Renal losses Extrarenal losses SIADH Intravascular vol Intravascular vol

Hypothyroidism
Diuretic excess gastroenteritis Glucocorticoid deficiency Hypoalbuminemia
Mineralocort excessive sweating Reset osmostat Cardiac Renal
deficiency failure failure
Nephritis: Third spacing: NS kwashiorkor
Salt wasting burns, pancreatitis Cirrhosis

UNa: >20 mmol/l <10mmol/l UNa >20mmol/l UNa: <10mmol/l <10mmol/l <10mmol/l >20mmol/l

USG/ UOsm :N or reduced increased increased USG/Uosm: increased increased increased USG 1.010

Rx: Isotonic saline Isotonic saline water restriction colloid salt and water restriction

USG – urine specific gravity UOsm –urine osmolality NS – nephrotic syndrome

SIADH (syndrome of inappropriate ADH secretion) – ADH induced water retention resulting in volume
expansion and natriuresis
• Diagnosed by low plasma Na and osmolality
• Urine not maximally dilute
• Normal renal function
• No evidence of inadequate Na intake or other source of Na loss
• Absence of water retaining drugs
• Absence of other causes of hyponatremia
• Treatment: - water restriction, hypertonic saline for acute neurological complication

41
• Drugs have no role in the management of SIADH in children
• Associated with pain, pulmonary disorders, CNS disorders, drugs e.g. Vincristine, Cyclophosphamide,
Indomethacin, Carbamazepine, Minoxidil, calcium channel blockers

Hypernatremia
Definition: serum Na >150mmol/l. Aetiological differentiation is aided by clinical presentation

Etiology:
1. Sodium overload: Salt poisoning, hyper aldosteronism t
2. Inadequate water:
• Inability to drink in response to thirst – comatose or neurologically impaired patients, infants, high
environmental temperatures, lack of free access to water
• Adipsia or essential hypernatremia:
- rare usually hypothalamic lesions
- no thirst in response to hypertonicity but ADH is released in response to non osmolar stimuli
- due to defect in ADH release in response to osmolar stimuli
- defect is destruction of the osmoreceptors but preservation of the supraoptic and
paraventricular nuclei where ADH is synthesized
- recurrent /persistent hypernatremia without thirst
- urine and plasma osmolality show no correlation
- ADH is however secreted normally in response to hypotension and hypovolemia
• Low set point for ADH release (reset osmostat)

3. Non renal water loss – without replacement

4. Renal water loss –

• Absence or inadequate secretion of ADH – central diabetes insipidus (DI) –head injury ,
infarction (Sheehan’s syndrome), tumours ( craniopharyngioma), histiocytosis, degenerative brain
disease, infections, hereditary (dominant), idiopathic
• Impaired tubular responsiveness to ADH – nephrogenic D: Chronic renal failure,
hypokalemia, hypercalcemia, damage to renal medulla –sickle cell disease, nephropathies, renal
papillary necrosis, chronic pyelonephritis/ reflux nephropathy, congenital
• Hereditary nephrogenic vasopressin resistant DI (VRDI) = congenital nephrogenic DI
2 types at the molecular level:
1. X linked –mutation in gene for tubular V2 ADH receptor
2. Autosomal recessive – mutation in gene for aquaporin 2 – the distal tubule water channel

Symptoms of hypernatremia: Restlessness, irritability, muscle twitching, hyperreflexia, seizures, coma and
death. History of polyuria, polydypsia, gastroenteritis, salt poisoning, renal disease, dehydration, growth
failure

Examination: growth parameters, BP, hydration status, conscious level, and temperature. Children with
hypernatremic dehydration appear less dehydrated than they really are, intravascular volume is preserved
until late in the illness, and the skin has a “doughy” feel.

Investigations: electrolytes, urea, creatinine, bicarbonate, glucose, calcium and albumin, Hb, serum
osmolality, spot urine – (ideally first morning void) for specific gravity, osmolality, microscopy and blood
protein

Hypernatremia may be complicated by hyperglycemia and hypocalcemia (see Hypernatremic

dehydration)

42
 Evaluation of hypernatremia

Clinical examination

Dehydrated Volume overloaded

Renal losses Extrarenal losses Increased total body Na

Sweat/ diarrhoea pure Na gain Na>H2Ogain

USG: < 1.005 <1.010 >1.015 > 1.015 <1.010

UNa+: Variable >20 variable UNa<10 UNa >20

(mmol/l)

Diabetes nonosmotic osmotic excessive sweating salt poisoning primary

Insipidus diuretics diuretics GI / respiratory losses NaHCO3- hyperaldos
overdose teronism

hypokalemia
hypertension

Rx: water replacement water+ salt replacement diuretics and treat primary
water condition
replacement

HYPERNATREMIC DEHYDRATION
• Risk of cerebral oedema if rehydration is too rapid
• Resusciation phase is as for other types of dehydration
• Calculated water deficit rather than % dehydration is a more accurate means fo determining fluid
deficit as ECF and plasma volume are preseved fro loner in hypernatremia, and clinical assessment
may under estimate the degree of dehydration

Fluid requirements see sections (1) (2), (3) (4) in the treatment of dehydration (page 2)
1. H2O deficit (litres) =
Na initial – Na desired x (0.6 x Wt in kg in children > 1 year of age)*
Na desired

*This represents total body water (TBW). In infants <1 year of age TBW = 0.75 x Wt in kg

Give water deficit over a period of days so that the serum sodium does not fall > 10mEq/l /24 hours

Fluids used D4.3 0.18 N saline, D5 in ½ normal saline, ORF, milk.

DO NOT USE SODIUM FREE SOLUTION

1 Maintenance : 75% of usual calculated maintenance since hypernatremia provokes ADH
secretion

43
 2 Ongoing losses: measured or estimated and replaced over 24 hours, every 4hours over the next 4
hours or as lost
3 N.B. subtract from the first 24 hours fluid the vomue used in resuscitation
4 Careful monitoring required. Repeat electrolytes at least every 12 hours. Reduce fluid intake if Na
falls too fast or increase if Na falls too slowly.
5 Salt poisoning with serum Na >200mEq/l may be treated with peritoneal dialysis with high
glucose (7.5%) and low Na dialysate

Potassium and bicarbonate replacement are as for other forms of dehydration.

Complications of hypernatremic dehydration: include hypocalcemia, hyperglycemia and seizures, so

check serum calcium and blood glucose regularly. Seizures may result from intracranial haemorrhage,
cerebral oedema or biochemical derangements.

Hypocalcemia: usually transient. If however symptomatic, start calcium infusion (See Disorders of
Calcium Metabolism).Remember that calcium and bicarbonate cannot be mixed.

Hyperglycemia: Is transient, does not require insulin and will resolve when hypernatremia is corrected.
Diabetes mellitus may be associated with hypernatremia and must be differentiated from the transient
hyperglycemia induced by hypernatremia. Hyperglycemia may cause underestimation of serum Na.

Correction of serum sodium for hyperglycemia

True serum Na mmol/l = [Blood glucose mmol/l] x 1.5 + measured Na mmol/l
5.5

POTASSIUM METABOLISM

• The combination of hypokalemia and high plasma bicarbonate is more likely due to K+ depletion
than primarily to metabolic alkalosis which is rare.
• Acute K+ loss causes more severe hypokalemia than chronic K+ loss
• The combination of hyperkalemia and low plasma bicarbonate is more likely due to metabolic
acidosis than primarily to K+ excess.

Hypokalemia (serum K+ < 3.5mmol/l)

Without K deficit: Familial periodic paralysis, athletes

With K deficit

• Reduced intake (UK+ <20mmol/l) - tea and toast diet, alcoholism, anorexia nervosa, starvation , clay
eaters, cellular incorporation of K in the treatment of megaloblastic anaemia, TPN
• Renal K+ loss – (UK+ > 20mmol/l
1. Increased activity of the Na/K exchange mechanism in distal nephron :
- Secondary hyperaldosteronism (hypertension associated)
- Cushings and steroids- mineralocorticoid effect on tubule (hypertension associated)
- Primary hyperaldosteronism
- ACTH treatment or ectopic ACTH production (hypertension associated)
- ? Bartter’s syndrome – normotension
2. Excess Na for exchange at distal nephron – diuretics inhibit Na reabsorption proximally
3. Reduced renal Na/H+ exchange --- increased Na/K exchange –a) carbonic anhydrase
inhibitors, b) renal tubular acidosis c)metabolic acidosis
4. Reduced proximal tubular K+ reabsorption --- renal tubular failure:
- polyuric phase of ARF,
- osmotic diuretic – DKA, mannitol (associated with dehydration and acidosis
- Fanconi syndrome

44
• Non renal K+ loss (UK+ <20mmol/l)
1. Intestinal secretions: prolonged vomiting, diarrhoea, intestinal fistulae
2. Reduced K intake: chronic starvation – reduced salt and water intake ---secondary
hyperaldosteronism
3. K redistribution: K loss into cells :glucose/ insulin, familial periodic paralysis (spontaneous K
entry into cells)
4. K loss from ECF by more than 1 route: alkalosis, pyloric stenosis and secondary alkalosis
Effects of hypokalemia
• metabolic – abnormal CHO metabolism, abnormal glucose tolerance, ? negative nitrogen balance
• hormonal – a) reduced aldosterone secretion, reduced insulin release
• vasoconstriction, rhabdomyolysis
• cardiac myogenic cell necrosis, myocardial fibrosis, ECG changes
• neuromuscular – ileus, weakness, quadraplegia, autonomic, insufficiency, postural hypotension
• renal: K conservation, polyuria, polydipsia, increased ammonia production, oedema and Na retention,
hypokalemic nephropathy

For K replacement
1gm KCl = 13mEqK+
Mist KCl : 10 ml = 13.4mEq
IV K+ at 10 mEq/hr does not require ECG monitoring
IV K+ at > 40mEq / hr should only be done with ECG monitoring

Treatment: There is no formula to estimate K deficit. Correction of hypokalemia consists of:

• providing maintenance K+ 2 mEq/kg/day (more in premature neonates0
• estimating and replacing on going losses (spot urine sodium, GI losses)
• estimating the deficit as a proportion of regular maintenance and replace by increasing maintenance by
50% or more depending of the severity of the hypokalemia
• regular measurement of electrolytes, losses and clinical status to assess response to treatment
• Treat the underlying cause of hypokalemia if possible

Hyperkalemia

In renal failure, serum K remains normal till GFR falls < 5mls/min
Symptoms and signs: weakness, paralysis, cardiac arrhythmias, partial depolarization (interferes with
neuromuscular transmission) – due to changes in extracellular ion concentration
Etiology:
Pseudo hyperkalemia – tourniquet, increased WBC, haemolysis
True hyperkalemia
1. Redistribution – acidosis, hyperkalemi, periodic paralysis, Digoxin toxicity
2. Reduced excretion – chronic or ARF, K sparing diuretics, reduced adrenal steroids (Addison’s disease,
hypoaldosteronism (TTKG)
Selective impairment of K excretion – SLE, renal transplant, SS.

Evaluation of Hyperkalemia

Renal function ------------------------- abnormal >>>>> renal failure

If normal check for metabolic acidosis

45
Present >> renal tubular acidosis –check UpH
>>mineralocorticoid deficiency –check TTKG = UK//U/P Osm
serum K+(See Chapter 1)
>> severe dehydration

If absent -perform Urinalysis

+hemastix >>>>>>>>>>> rbc on microscopy – true haematuria – renal disease
>>>>>>>>>>> no rbc on microscopy – check for hemolysis

serum not haemolysed >>>>>>>>>>> myoglobinuria

serum haemolysed >>>>>>>>>>>>>>haemoglobinuria

Treatment:
General: See Chapter 10
Specific: Treat cause

POLYURIA
Definition: Passage of abnormally large urine volumes (>4cc/kg/hr)

Etiology
• Excessive water intake e.g. psychogenic polydipsia
• Excessive water output – diabetes insipidus
• Excessive urinary solute load e.g. diabetes mellitus, osmotic diuretics, salt wasting syndromes –
nephropathy or mineralocorticoid deficiency, diuretic phase of renal failure (urea loss), hypercalcemia
(calcium loss)

History: Predisposing factors as above, salt craving, diuretic use, fluid intake, urine volume. Distinguish
between polyuria and increased frequency of micturition without polyuria.
Examination: Growth parameters, blood pressure, hydration status, visual fields and CNS examination,
and genitalia for ambiguity.

Investigations:
• Urine volume/24 hour or as a single void
• Urine dipstix : glucose, protein, blood / microscopy (spun) – cells , casts / specific gravity and
osmolality –random or water deprived
• Urine pH (by electrode in Chem. Pathology) – RTA
• Hb, urea, electrolytes, creatinine, bicarbonate, calcium, albumin (glucose of glycosuric)
• If central DI : cranial CT, visual fields, SXR, T4, TSH, R3RU, a.m. and p.m. cortisols +/- growth
hormone
• If nephrogenic DI – estimate creatinine clearance and protein excretion from spot urine and serum
values ( see Chapter 1 – Assessment of Renal Function), renal ultrasound +/- IVP, +/- renal scan

To calculate Uosm (urine osmolality) from USG

Uosm (mOsm/kg H20 ) = (USG – 1.000) x 40,000

46
 EVALUATION OF POLYURIA

Measure urine volume

Single void

Normal to low High

Increased urinary frequency Possible polyuria

Not polyuria

Random USG

< 1.005 1.010

Diabetes insipidus / psychogenic polydipsia Could be normal

Water deprivation test Overnight fast

USG < 1.005 USG >1.012 USG 1.010 USG > 1.015

Diabetes insipidus (DI) Normal Renal disease Normal

or
Possible psychogenic polydipsia
Vasopressin stimulation

USG increased USG unchanged

UVol decreased UVol unchanged

Central DI Nephrogenic DI

Rx: Vasopressin Rx: Low salt diet, Indomethacin or Hydrochlorothiazide

USG – Urine specific gravity UVol – urine volume

NB: If results are equivocal request Endocrine or Nephrology consultation

WATER DEPRIVATION TEST

The water deprivation test (standard 9 hours and prolonged 17 hours) is used to differentiate between
diabetes insipidus and psychogenic polydipsia. The indications include polyuria, polydipsia and a low urine
specific gravity.

Standard
Patient has:
• No fluids after 6 a.m.
• Dry breakfast by 7.30a.m
• NPO at 8.00a.m. for test duration

47
Prolonged
Patient has:
• No fluids after 10.00p.m.
• Dry breakfast by 7.30 a.m.
• NPO at 8.00a.m. for duration

Standard:
• Vital signs – pulse, resp. rate, BP - q1hourly
• Patients to be weighed at start of test
• Infants (<3 years) –weighed hourly
• Children> 3 years) –weighed 3 hourly
• Urine samples to be taken at start of test
• Infants – catheterize and so samples q 2 h
• Children – test each sample voided
• Urine tested for specific gravity, glucose and protein- volume recorded
• Blood samples – taken at 9.00a.m. and 3.00 p.m. and 4.p.m.
• Tests requested – blood, urea, electrolytes, glucose in order to calculate serum osmolality (POsm)

To calculate Serum osmolality (SOsm)

SOsm (mOsm /kg H20) = (Na (mmol/l) x 2) + urea (mmol/l) + glucose (mmol/l)

Prolonged:
• Should not be done on an infant or a child who is strongly suspected clinically of having DI
• It is useful in differentiating partial DO from psychogenic polydipsia
• Urine samples taken at start of test and then 4 hourly until 8.00 a.m. then follow standard protocol. All
urine volume recorded
• Vital signs q4 h overnight then follow standard protocol
• Weigh at start of test
• Blood sample at 10.00 p.m. and 6.00a.m. then follow standard protocol
• At 3.00 p.m. if patient has been unable to concentrate urine > 1.012 then give:
a) Aqueous Pitressin (1:1,000) – 0.1 unit /kg to a maximum of 5 units IM
OR
b) DDAVP 0.1 ml intranasally
The IM route is preferred.
• At 1 hour and 2 hours after exogenous ADH (above) do:
• Urine samples for specific gravity, glucose, protein
• Blood samples for urea and electrolytes and glucose
• NB – discontinue test if :
a) Weight loss >3%
b) Patient becomes hypotensive with postural hypotension
c) Patient becomes distressed

Results of Water Deprivation Test

• Central DI: SOsm increased Serum Na increased USG low. After ADH –USG
increases
• Nephrogenic DI : SOsm increased Serum Na increased USG low. After ADH – USG still
low
• Psychogenic polydipsia urine concentrates slowly as dehydration occurs

48
References:
1. Disorders of Water Metabolism. Schrier RW, Berl, T in Renal and Electrolyte Disorders (1980) 2nd
edn. Shrier ed. Little Brown and Company, Pub.
2. Serum sodium abnormalities in children. Ped Clin N Am (1982) 29: 907-932
3. Differential diagnosis of polyuria and diabetes insipidus. Singer I, Med Clin N am (1981) 65: 303-320
4. Pediatric Nephrology (1999)p 133-141. 4th edn. Barratt, Avner, Harmon eds. Lippincott, Williams and
Wilkins pub
5. Clinical Chemistry in Diagnosis and Treatment (1975) p 30-74. Zilva J, Pannall PR.

49
 CHAPTER 7

UROLITHIASIS AND DISORDERS OF CALCIUM METABOLISM

Etiology
1. Calcium lithiasis (commonest)
• Normocalcemic hypercalciuria
• Idiopathic hypercalciuria – absorptive or renal
• Distal renal tubular acidosis
• Drug induced (Furosemide)
• Hypercalcemic hypercalciuria
• Increased calcium reabsorption from bone – primary hyperparathyroidism, immobilization,
adrenocorticosteroid excess, adrenal insufficiency, osteolytic metastases
• Increased GI absorption e.g. hypervitaminosis D, idiopathic hypercalcemia of infancy,
sarcoidosis , milk-alkali syndrome
2. Hyperoxaluria
• Primary – autosomal recessive.
• Type 1 more severe than type 2 – associated with glycollic aciduria and renal failure
• Type 2 –with glyceric aciduria
• Secondary
• Dietary oxalate excess
• Hyperabsorption of oxalate – intestinal disease (inflammatory bowel disease) , lowered
intestinal Calcium levels
• Excess ascorbate (Vit C) intake
• Ethylene glycol ingestion
• Methoxyflurane anaesthesia
• Aspergillosis
• Vitamin B6 deficiency
• Mild metabolic hyperoxaluria
3. Hypocitraturia
Seen in distal RTA, malabsorption syndromes associated with enteric hyperoxaluria. Citrate is a
urinary stone inhibitor. Citrate excretion is reduced by thiazide diuretics, acidosis and hypokalemia.
4. Uric acid lithiasis / hyperuricosuria
Often associated with calcium oxalate stones. Predisposing factors; urine pH <6, decreased fluid
intake, hyperuricemia (gout, Lesch Nyan syndrome, tumour lysis syndrome)
5. Struvite (infection, triple phosphate) lithiasis – magnesium, ammonium phosphate and calcium
phosphate (apatite) – sometimes staghorn calculi -associated with urinary tract infections caused by
urease producing organisms
6. Inborn errors of metabolism
• Cystinuria – inborn error of metabolism – diagnosed by aminoaciduria of Cystine, Ornithine,
Arginine and Lysine
• Hereditary xanthinuria, / Orotic aciduria
7. Drug related
8. Hypomagnesuria (magnesium is and inhibitor of Calcium oxalate stone formation
9. Chronic hypovolemia

History

50
 • Pain, haematuria, fever, UTI symptoms, failure to thrive, history of recurrent UTI, especially with
Proteus, recurrent abdominal pain especially in the flank with loin to groin radiation. Recurrent or
persistent gross haematuria (idiopathic hypercalciuria is a common cause).
• Positive family history of renal stones
• Ask re: diet, excessive Vit C and D intake, drug ingestion
• High oxalate foods: cocoa, Ovaltine, tea, green beans, beets, celery, eggplant, okra, green peppers,
spinach, all kinds of berries, purple grapes, fruit cocktail, oranges, orange peel and orange juice,
tangerine and tangerine juice, fruitcake, grits, wheat germ, nuts - almond, pecans, cashews,
peanuts and walnuts, chocolate – cocoa, vegetable soup, tomato soup, marmalade.

Examination
Growth parameters, blood pressure, abdomen for masses e.g. distended bladder or kidneys.

Investigations
Urine –
• Cleaned – MSU for culture, unspun for microscopy, urinalysis for crystals, pH, blood, protein, wbc
and rbc
• Spot urine X 3 for calcium, uric acid, creatinine, one of which should include a spot urine phosphate
which can be combined with the serum phosphate and serum creatinine to calculate the tubular
reabsorption of phosphate TRP
• If absorptive hypercalciuria is to be distinguished from renal hypercalciuria, do spot urine
calcium/creatinine on early morning fasting urine sample. This is just a screening test.
• Spot urine for amino acid screen (Chemical Pathology)– to rule out cystinuria and other
aminoacidurias
• 24 hour urine oxalate (and creatinine on the same sample if possible in the lab) – done abroad privately
• 24 hour urine uric acid and creatinine, 24 hour urine calcium (and creatinine if possible in the lab) – to
verify the increased urinary excretion documented on spot urines or to prove excess urine solute
excretion where suspected but unproven by spot samples. 24-hour urine creatinine with the measured
solute helps to assess completeness of the collection. 24-hour urine calcium –collected in acid washed
bottle.
• +/- 24 hour urine citrate and creatinine
• stone analysis

Blood: urea, creatinine, electrolytes, bicarbonate, calcium (without tourniquet), phosphate, alkaline
phosphatase, serum albumin, uric acid , (PTH levels if available)
Radiology;
• Plain abdominal X-ray (about 90% of stones are radioopaque – calclium oxalate, calcium phosphate,
struvite stones). Cystine stones are less opaque and uric acid stones are non opaque
• Renal ultrasound – for obstruction and stone visualization – pyelectasis takes >6 hours to develop- U.S
is less sensitive than plain XR for stone visualization
• Intravenous Urogram (IVU) – for stone localization – the best test. In acute ureteral obstruction there
is a delayed dense nephrogram. On delayed films, there is renal enlargement and pyelo and caliectasis
+/- ureterectasis
• CT scan of kidneys – for oxalate, phosphate, struvite, cystine, uric acid calculi.
• Doppler US – urine jet from ureteric orifice into the bladder suggests stone is non obstrucitve – not
always reliable
• +/- MCUG if urological abnormalities likely
• If hyperparathyroidism or rickets present – X ray L wrist bone age and L hand penetrated view for
rickets and evidence of hyperparathyroidism

Tubular reabsorption of phosphate (see normal values) –

Normal >80% Hyperparathyroidism <80%

51
Normal Urinary Solute Excretion rates .
Calcium < 0.1mmol/kg/day <4mg/kg/day

Urine calcium:creatinine ratio < .00074mmol/l:umol/l <0.21:1 mg/dl:mg/dl

Uric acid < 0.06 mmol/kg/day <815mg/1.73m2/day

<35mg/kg/day
Urine uric acid:creatinine ratio <0.00067 mmol/l:umol/l

Oxalate < 0.46mmol/1.73m2/day < 1year age:<0.21mg/mg/creatine

Oxalate:creatinine ratio
1-12 years: <0.12mg/mg creatinine
>12years: <0.07mg/mgcreatinine
< 2mg/kg/day
In primary hyperoxaluria In primary hyperoxaluria
24 hr urine oxalate 24 hr urine oxalate
>1mmol/1.73m2/day >100mg/ 1.73m2/day
0.00012mmol/l:umol/l 0.08 mg/dl:mg/dl

Cystine <75mg/g creatinine

Citrate >180mg/g creatinine

Magnesium > 88mg/1.73m2/day

Creatinine* 135-175umol/kg/day (child

and adult female)
175-220umol/kg/day (adult
male)
Creatinine clearance >80ml/min/1.73m2

*low creatinine excretions suggests incomplete collection

Handbook of Pediatric Urology (1997) p237. Baskin, Kogan, Duckett, eds.
Stone Disease – Diagnosis and Management (1987), p320. SN Rous SN,ed.
Pediatric Nephrology 4th Edn (1999) p938 Barratt, Avner, Harmon, eds.

Conversion factors:
• Urate (g/day) x 5.948 = mmol/day
• Oxalaate (mg/day) x 11.11 = µ mol/day
• Creatinine (g/day) x 8.89 = mmol/day
• Cystine (mg/day) x 4.161 = µ mol/day
• Calcium (mg/day) x .02495 = mmol/day

Management
Medical:
• Acute presentation: Analgesic (e.g. Baralgin), adequate hydration IV or po with 1 ½ - 2 times
maintenance fluid. If renal failure or significant obstruction present, these must be addressed
specifically and fluid management adjusted as appropriate. Antibiotics if UTI suspected.
Catherization of bladder if bladder outlet obstruction. Nephrology and Urology consultation.
• Maintenance therapy

52
 • General :
• Relief of obstruction, removal of stones
• High fluid intake at least 1 ½ times maintenance fluids
• Follow up plain abdominal X-rays for further stone formation (if opaque), with renal
ultrasound for evaluation of persistent of obstruction, progressive nephrocalcinosis or
urolithiasis every 6 months – 1 year.
• Monitor excretion of urinary solute by spot urines and/or 24 hour urine collections every 3 – 6
months after starting treatment to determine if treatment is adequate.
• Specific:
Idiopathic hypercalciuria: In children, the distinction between absorptive and renal hypercalciuria tends
to be more theoretical than practical. Both are most commoly treated as follows.
Low sodium intake
1. High fluid intake (1 ½ - 2 times maintenance)
2. Thiazide diuretics – reduces calcium excretion in both absorptive and renal hypercalciuria.
Hydroclorothiazide 2 mg/kg/day or Bendrofluazide 0.2mg/kg/day (if urolithiasis present), however if
haematuria is the only presentation of hypercalciuria, chronic thiazide therapy is not absolutely indicated).
Side effects – hypokalemia, hyperuricemia, dehydration
• Follow-up blood urea, creatinine, electrolytes and creatinine and uric acid
• Monitoring as above

Hypercalciuria:
• with hypercalcemia – treat hypercalcemia and its cause
• with distal RTA – treat acidosis ideally with potassium citrate.

Uric acid calculi

• Dietary purine restriction
• High fluid intake
• Alkalinize the urine preferably with K citrate rather than Na bicarbonate to reduce risk of calcium
oxalate stone formation – pH should be 6-6.5. Give doses throughout the day with the last dose at
bedtime. If urine pH >7, risk of precipitation of calcium phosphate.
• K citrate (mist pot cit) 1 –3 mEq/kg/day divided t.i.d
• Na bicarbonate 1 –2 mEq/kg/day divided t.i.d.
• Allopurinol (for hyperuricemia, or recurrent uric acid stones despite other measures of control)
• Allopurinol 5 -10 mg/kg/day(t.i.d)
Treat concomitant hypercalciuria if present and monitor uric acid excretion and renal function as described
or hypercalciuria.

Hyperoxaluiria – General : dietary oxalate restriction and high fluid intake, treat bacterial overgrowth,
underlying bowel disease, and uric acid calculi if present. Monitor renal function and oxalate excretion
periodically as described for hypercalciuria.
• Primary hyperoxaluria – reduce dietary oxalate, hydrochlorothiazide 2 mg/kg/day, large doses of
inorganic phosphate ( if no renal failure), Pyridoxine, possibly magnesium oxide.
• Enteric hyperoxaluria – reduce dietary oxalate, give aluminum hydroxide and cholestyramine to
reduce oxalate absorption), K citrate, Mg and Ca supplements
• Hyperuricosuric calcium oxalate stones – low sodium diet, increased fluids, dietary purine (protein)
restriction, allopurinol if intolerant of dietary restriction, K citrate supplements to inhibit Ca oxalate
crystal formation (Urologic Clinics of North Am 1997)

Struvite calculi
• Surgical removal
• Treat infection – 1-2 weeks of therapeutic antibiotics, followed by prophylaxis at 50% of the usual
dose for 3 months. Monthly urine cultures. When sterile for 3 months discontinue prophylaxis.
• ?urease inhibitors

53
Cystine calculi –
• very high fluid intake day and night, aiming for urine output of 2 litres (child), 3 – 4 litres (adults)
• Alkalinization till urine pH is >7.5 in the morning
• Na bicarbonate 2 –3 mEq/kg/day (t.i.d. – q.i.d)
• K citrate 1 –3 mEq/kg/day (t.i.d. – q..i.d)
• D penicillamine30 mg/kg/day (given q.i.d.) – used to dissolve stones when alkalinization and increased
fluids have failed. Supplement with vitamin B6
Monitor renal function and cystine excretion periodically to assess adequacy of therapy.

HYPOCALCEMIA
Definition:
(a) Full term – serum calcium <1.9mmol/l
Preterm - serum calcium <1.7 mmol/l
Older child –serum calcium <2mmol/l
Or Ionized calcium <0.75mmol/l
[Residents Handbook of Pediatrics (1987) p 398]

Etiology
• Neonatal period – prematurity, low birth weight, Di George syndrome, severe sepsis, intracranial
haemorrhage, diabetic or hyperparathyroid mother, poor calcium intake, transient neonatal
hypoparathyroidism, exchange transfusion.
• General – Vitamin D deficiency, renal failure, steatorrhoea, steroid or furosemide therapy, hypo – or
pseudo hypoparathyroidism

Treatment
a) If symptomatic e.g. seizures, tetany, this is an emergency. Treat by IV route only.
b) IV calcium at 0.2 mEq Ca2+/kg/hr
c) Repeat serum calcium level 4 hours after starting the infusion and adjust according to value. Once
serum calcium level is >2mmol/l, reduce infusion rate slowly . Increase infusion rate if serum calcium
falls. Start measures (d) and (e) and attempt to wean off IV when serum calcium normalizes
d) Start oral calcium at 2 mEq/kg/day
e) Rocaltrol (Calcitrio) 1,25 dihydroxy Vitamin D3
• Newborns 0.10 – 0.15 ug/kg/day reduced to 0.025 –0.05ug/kg/day after 3 –4 days
• Older children 0.025 – 0.05ug/kg/day

Watch that IV calcium does not extravasate as serious burns may occur. Never give Calcium IM or
subcutaneously

IV Calcium infusion: using 10% Calcium gluconate (any other intravenous Calcium preparation may be
used but the volume of the preparation required to deliver 0.2mEq/kg/hr must be calculated for each
product).
To deliver 0.2mEq/kg/hr of 105 Calcium gluconate :
• Make a 1:5 dilution of 10% Calcium gluconate with 5% glucose water = 0.1mEq Ca2+ /ml
• Calcium dose in this dilution = 2cc/kg/hr (0.2mEq/kg/hr)

HYPERCALCEMIA
Definition: serum calcium >3mmol/l
Treatment:
1. If secondary to Vitamin D or Calcium supplements – discontinue immediately
2. Low calcium diet
3. Fluids at 2 ½ times maintenance – usually as normal saline
4. Corticosteroids e.g. hydrocortisone 4 mg/kg/dose IV q 4 – 6 hourly
5. Furosemide 0.5 – 1 mg/kg IV q 4 –6 hourly (avoid dehydration)

54
6. Watch for hypokalemia, hyponatremia,
7. Monitor serum calcium and electrolyte levels frequently

Some calcium salts and their approximate calcium content

Table gives the amount of elemental calcium per gram of preparation, so in order to calculate the # mEq
Ca2+ in your preparation, the # mg of CaCO3 per unit of preparation must be known.
e.g Regular Tums – 500mg CaCO3 / tablet
- 1 gm CaCO3 / 2 tablets = 20mEq Ca2+
- 1 tablet = 10mEq Ca2+

Approximate calcium content per g

Calcium salt mg mmol mEq

Calcium acetate (anhydrous) 253 6.3 12.6

400 10.0 20
Calcium carbonate
273 6.8 13.6
Calcium chloride (dihydrate)
211 5.3 10.5
Calcium citrate(tetrahydrate)
66 1.6 3.3
Calcium glubionate(monohydrate)
82 2 4.1
Calcium gluceptate(anhydrous)
89 2.2 4.5
Calcium gluconate (monohydrate)
191 4.8 9.5
Calcium glycerophosphate ( anhydrous)
184 4.6 9.2
Calcium lactate (anhydrous)
147 3.7 7.3
Calcium lactate (trihydrate)
130 3.2 6.5
Calcium lactate(pentahydrate)
129 3.2 6.4
Calcium lactate gluconate (dihydrate)
51 1.3 2.5
Calclium lactobionate (dihydrate)
131 3.3 6.5
Calcium laevulinate (dihydrate)
233 5.8 11.6
Calcium hydrogen phosphate (dihydrate)
388 9.7 19.3
Calcium phosphate (Ca3(PO4)2)
399 10.0 19.9
Calcium phosphate (10CaO. 3P2O5.H2O)
135 3.4 6.7
Calcium pidolate (anhydrous)
78 1.9 3.9
Calcium sodium lactate( tetrahydrate)

Martindale* – the Extra Pharmacopoeia – 31st Edition 1996 page 1178

55
References:
1. Stone disease diagnosis and management. (1987) pp 150, 182, 347 –378. Rous SN ed. Grune and
Stratton –pub.
2. Urolog Clin N Am (1997) 24: 135-147, 147 –162, 81-86, 97-116
3. Pediatric Nephrology (1999) pp 938-939. 4thedn. Barratt TM, Avner ED, Harmon WE eds. Lippincott,
Williams and Wilkins pub.
4. Pediatric Nephrology (1989) 3::317 –331
5. Martindale – The Extra Pharmacopoeia (1996) 1178. 31st edn.

56
 CHAPTER 8

URINARY TRACT INFECTIONS

DEFINITIONS:
Urinary Tract Infection (UTI):
• Significant bacteriuria with or without urinary tract symptoms
Asymptomatic bacteriuria:
• Significant bacteriuria without symptoms
Acute cystitis:
• Symptomatic UTI localized to the bladder
Acute pyelonephritis:
• Symptomatic UTI localized to the renal parenchyma
Significant bacteriuria:
• Any growth on a bladder tap urine sample (except up to 2,000 -3,000 colonies /ml of coagulase
negative staph
• > 103colonies /ml (catheter sample - CSU) in a normal child
• > 105 colonies /ml in a CSU from a child on clean intermittent catherization (as per voided urine below
• > 105 colonies /ml of voided urine (MSU or clean catch urine) on > 2 voided samples showing the
same organism with the same sensitivity

Pyelonephritis : is present in >75% of children < 5 years of age with febrile UTI, and causes renal scarring
in 24-64% of children < 5 years of age with UTI. Most UTI's resulting in scarring or reduced renal growth
occur in children <age 4 years. Children < age 3 years often have recurrent infections (up to 1/3 of which
are asymptomatic) and therefore are at greater risk of renal scarring.
Focal renal scarring secondary to childhood pyelonephritis results in: 23% risk of hypertension, 10%
risk of end stage renal disease (ESRD), 13% risk of toxaemia in pregnancy.

AETIOLOGY OF UTI:
• GRAM NEGATIVE
• E. coli*, Klebsiella, Proteus, Pseudomonas, Enterobacter, Citrobacter, Morganella, Serratia,
Providentia
• GRAM POSITIVE
• Staphylococcus, Enterococcus
PREDISPOSING FACTORS:
• Host factors - obstruction (mechanical / neurogenic), vesicoureteric reflux, constipation, voiding
dysfunction, foreskin, hypercalciuria / stones, parasites
• Host -non factors - improper wiping, bubble bath
• Bacterial factors - adherence factors, capsular antigen, haemolysin, resistance to serum
bactericidal activity

HISTORY:
• Straining, poor stream - outlet obstruction
• Gait disturbance, enuresis, encopresis - neurogenic bladder
• Constipation, urgency, enuresis, squatting - dysfunctional voiding
• Recurrent PUO - unrecognized UTI
• In neonate - sepsis, jaundice, failure to thrive, vomiting, straining with micturition, haematuria
• In older child - frequency, dysuria, enuresis, fever , offensive urine, haematuria, loin pain
EXAMINATION:
• Growth parameters, anaemia - chronic illness
• Blood pressure - hypertension
• Abdominal examination - obstructive uropathy, constipation
• External genitalia - meatal stenosis, labial adhesions, vulvovaginitis
Sacral anomalies, anal wink, lower limb reflexes - neurogenic bladder

57
DIAGNOSTIC PITFALLS - symptoms/signs incorrectly suggestive of UTI
• Pink diaper syndrome - amorphous urates on diaper - salmon coloured powder
• Normal straining sounds during infant voiding
• Urethritis, vulvovaginitis
• Dysfunction voiding - small bladder, unstable bladder, large bladder - may have frequency, urgency,
enuresis
• Daytime urgency, frequency syndrome (hysterical voiding of childhood) - daytime urinary frequency
without enuresis- emotional in aetiology

INVESTIGATIONS:
Urine culture -
• preferably bladder tap (children <2 years) or CSU if only a single sample is possible before starting
antibiotics
• CONTRAINDICATIONS TO BLADDER TAP:
1. Patients e.g. cardiacs for whom infective endocarditis prophylaxis would have been needed
for genito-urinary instrumentation
2. Patients with coagulopathies eg haemophilia
3. Patients with pelvic kidney
4. Empty bladder
• CONTRAINDICATIONS TO CSU
• Patients in category (1) above
• Infections of the genital / peri - urethral area

Voided urines have a high false positive rate and are conclusive only if negative. If voided urines are used
to diagnose UTI, there should be at least 2 samples, both showing the same organism with the same
sensitivity pattern. The external genitalia should be cleaned and wiped dry. When a urine bag is applied it
should be changed at least every 30 minutes to avoid external contamination.

Samples collected should be processed promptly. If there is a delay in delivery to the laboratory, the sample
should be refrigerated to avoid bacterial multiplication, and false positive results. Samples should be
processed within 48 hours of collection.

Immediate diagnostic aids - these aid with the diagnosis but only a urine culture can diagnose a UTI:
• Multistix (Ames ) + test for leukocytes, nitrates and >trace blood - suggestive of UTI
• Urine microscopy - any bacteria on an uncentrifuged sample is highly suggestive of UTI
• Haematuria and / or pyuria do not = a UTI
• UTI may be present without pyuria

SUPPLEMENTAL TESTS
Blood urea, creatinine, electrolytes, CBC (+/- Hb electrophoresis), (+/- Blood culture)

UTI controversies re: investigation:

In the First World where full investigation for UTI from infancy has been practiced for at least a decade,
the recommendation now is that no radiological imaging is required in children > 2 years of age with the
clinical diagnosis of cystitis (acute dysuria, without high fever, with normal concentrating ability) if there is
no suspicion of UTI in the history and if there is a high detection rate of infant pyelonephritis in the
community. (Hansson s, Joday U - Pediatric Nephrology 4th edition 1999 - 844). In Jamaica infant UTI's
are still being missed or uninvestigated. The policy of no imaging studies in the girls < 2 years is based on
the observation that radiological abnormalities are rarely seen in this group, but, in societies, like Jamaica,
with a low detection rate of UTI's in infants and small children, it must be stressed that children with
previously undetected UTI and renal scarring or vesico-ureteric reflux may present later with afebrile
symptomatic infections, and would be missed if this protocol is applied to Jamaica. Therefore IN
JAMAICA, for the time being, ALL CHILDREN WITH UTI REQUIRE RADIOLOGICAL
INVESTIGATION.

58
 ABOLUTE ESSENTIALS:
• All children (males and females)must be investigated, after the first UTI
• Ensure that the diagnosis of UTI is based on strict culture criteria and not just on symptoms or
diagnostic aids alone

AIMS OF INVESTIGATION:
• Diagnose obstructive uropathy eg - PUV, PUJ and VUJ obstruction, neurogenic bladder
• Diagnose vesico-ureteric reflux (16% of Jamaican children with UTI have VUR )
• Obstructive uropathy, reflux nephropathy, renal dysplasia account for 59% of the cases of childhood
CRF in Jamaica at UHWI (Dec1984-- October 1996)

RADIOLOGICAL INVESTIGATIONS:
• Renal ultrasound (all children) - request renal lengths and compare with age and weight related
normal values (see Chapter 1)
• Micturating cystogram (MCUG) - contrast
• Age <5 years or any age if abnormal examination or abnormal renal ultrasound
• Performed when the urine is sterile
• ALWAYS LOOK AT THE MCUG YOURSELF - IF IT LOOKS ABNORMAL - eg dilated
or irregular posterior urethra or bladder - DISCUSS WITH PAED NEPHROLOGIST / PAED
SURGEON
• Renal scan (DMSA)- renal scarring, or (locally available) Glucoheptonate renal scan- renal
scarring and function
• To assess renal function, detect pyelonephritis and renal scarring
• Indications: abnormal MCUG or ultrasound , recurrent UTI, febrile UTI, suspected acute
pyelonephritis
• If obstruction suspected request Glucoheptonate renal scan with Lasix
• Indirect radionucleide cystography - voiding phase of the renal scan - in children who can void on
request - is the most sensitive means of detecting vesico-ureteric reflux, but does not give good
anatomical definition so cannot replace the standard MCUG
TREATMENT -
Supportive - analgesics, increased fluids, correct underlying cause, correct constipation
LOWER UTI (CYSTITIS) - see table
• Broad spectrum antibiotics - Trimethoprim / sulphamethoxazole, Amoxil, Augmentin, oral
cephalosporins, Sulphonamides, Nitrofurantoin
• Duration of treatment controversial - conventional treatment - 10 days - RECOMMENDED
• Shorter courses : single dose, 1,3, or 5 days - only for uncomplicated ITO (normal tracts) , not for the
first UTI, higher recurrence rate and need good follow-up I DO NOT RECOMMEND THE
ABBREVIATED ANTIBIOTIC COURSES

ORAL TREATMENT OF UTI

Amoxacilllin 40-50mg/kg/dy (t.i.d.)
Amoxil Clavulinate (Augmentin) 50mg/k /dy (bid)- AUGMENTIN bd preparation
50mg/kg/dy (t.i.d.) - Generic CURAM
Cephalosporin
Cefixime 8mg/kg/dy (b.i.d.)
Cefpodixime 10mg/kg/dy (b.i.d.)
Cefproxil 30mg/kg/dy (b.i.d.)
Cephalexin 50-100mg/kg/dy (q.i.d. or t.i.d)
Loracarbef 15-30mg/kg/dy (b.i.d.)
Cefuroxime 60mg/kg/dy(b.i.d.)
Cefaclor (Ceclor) 40mg/kg/dy (t.i.d.ApoCeclor , b.i.d. Ceclor)
Nitrofurantoin * not in infants<6 weeks and in renal failure 3mg/kg/dy(q.i.d)

59
 ACUTE PYELONEPHRITIS - see table
Outpatient management
• Nontoxic children and infants > 3 months old
• If compliance expected
• Initial 1-2 days of long acting 3rd generation Cephalosporin (IM Ceftriaxone), then 10-14 days of oral
antibiotics, or total of 10 - 14 days of parenteral antibiotics depending on severity and clinical progress.
In patient management
• Toxic children and infants < 3 months old
• Amoxil and an aminoglycoside or new 3rd generation Cephalosporin eg Cefotaxime, Ceftriaxone
• Parenteral 10 -14 days ( neonate)
• Parenteral till afebrile for 1-2 days then po to complete 10-14 days or parenteral for total of 10-14 days
depending on severity of illness and clinical response.

PARENTERAL TREATMENT OF UTI

Ceftriaxone 20 –50mg/kg od /dy (age 1-14 days)

75mg/kg/dy (o.d. or q 12 h) (age15 days – 1 2 years)
1 – 2 g /dy (od ) (adult or weight > 50 kg)

Cefotaxime 150mg/kg/dy (q6h-q8h)

Ceftazidime (covers Pseudomonas and Enterobacter) 150mg/kg/dy(q6h-q8h)
Cefazolin 50mg/kg/dy (q8h)
Gentamycin 5-7.5mg/kg/dy (q12-8h)
Tobramycin 5mg/kg/dy (q8h)
Ticarcillin 300mg/kg/dy )q6h)
Ampicillin 100mg/kg/dy (q6h)
Augmentin 30mg/kg/dy (q8h) (older infants and children)
30mg/kg/dy(q12h) (prems and full terms in perinatal period)

FOLLOW-UP INVESTIGATIONS
• Urine culture - 2 days after starting, 2 days after ending treatment and at intervals thereafter for about
1 year
• Monitor urea, creatinine and electrolytes when treating acute pyelonephritis especially with
aminoglycosides
• After 1st UTI treatment has ended, start antibiotic prophylaxis until
• investigations have been completed and found to be normal
• until age 1 year in infants < 1 year (high risk of renal scarring)
Indications;
• vesico-ureteric reflux
• recurrent symptomatic UTI (>3/year)
• obstructive uropathy, voiding dysfunction
• before initial radiological evaluation
• neonates and infants <1 year with febrile UTI and inflammatory changes on renal scan (scar risk)
• Drugs - neonates: Amoxil, Cephalosporins, Older child - Cotrimoxazole, Nitrofurantoin (mainly)

60
 PROPHYLACTIC ANTIBIOTICS

Trimethoprim /SMX 2mg TMP / 10mg SMX /kgnocte

Trimethoprim 2mg/kgnocte
Nitrofurantoin 1-2mg/kg nocte
Sulphisoxazole 10-20mg/kg/dy (b.i.d)
Nalidixic acid (not neonate) 30mg/kg/dy (b.i.d.)
Cefadroxil (Duricef) 3-5mg/kg/dy (nocte)
Cefalexin (Ospexin) 125mg or 250mg nocte (up to 15 mg/kg nocte)
10mg/kg nocte (neonates)
Amoxil 25mg/kg/dy (bi.d) - neonates
Ciprofloxacin 1mg/kg/dy(nocte)
Pivmecillinam 3-5mg/kg/dy
Pivmecillinam/pivampicillin 3-5mg/kg/dy (Pivmecillinam)

INDICATIONS FOR REFERRAL

• Abnormal physical examination or investigations
• Recurrent UTI
• Refer to Paediatric surgeon / paediatric urologist : obstructive uropathy
• Refer to Paediatric nephrologist - all other pathology
• Always ask for advice if uncertain of management
• DO NOT REFER EVERY CHILD WITH UTI TO POPD Renal - ONLY THOSE WITH
PROBLEMS

References:
1. Pediatrics (1999) 103:843-852- American academy of Pediatrics - Committee on Quality Improvement
- subcommittee on Urinary Tract Infection
2. Pediatric Nephrology 4th edition Barratt, Avner and Harmon editors (1999): 835-850
3. Pediatr Clin N Am (1997) 44:1133- 1169. Urinary Tract Infections in Children. Epidemiology,
evaluation and management.
4. Pediatr Clin N Am (1997) 44: 1171-1190.Vesicoureteral reflux

61
 CHAPTER 9

ENURESIS AND OTHER VOIDING DISORDERS

Definition:
The involuntary passage of urine in a child old enough to have attained bladder control.
Approximately 98% of children are dry by day at age 4 years and 70% are dry by night at that age.

Nocturnal enuresis – uncontrolled micturition during the night in a child over the age of 5 years, occurring
> once /week.

Diurnal enuresis – daytime wetting beyond the age of 5years – the age beyond which reliable daytime
dryness is expected to have been achieved.

Enuresis
Classification :
• Diurnal
• Nocturnal
• Diurnal and nocturnal
All of the above subdivided into:
• Primary – incontinence in a child in whom bladder control has never been attained
• Secondary – incontinence 6 months to 1 year after continence has been achieved

NOCTURNAL ENURESIS
Primary : - Incidence : 10% of 5 year olds are wet at night but only 1% of 15 year olds have this problem.
It resolves spontaneously with time – 15% of bedwetters over the age of 6 years will become dry each year
without intervention (spontaneous cure rate of 15% after age 6 years).

Another classification of nocturnal enuresis is based on EEG and cystometric readings during
nocturnal enuresis (Scan J Urol Nephrol, Vol31,1997, Suppl 183 (7-10).
• Type 1 -due to mild arousal disturbance. When the bladder becomes full during sleep, there is
evidence of arousal on the EEG, but enuresis occurs without the subject awakening (no inhibitory
central response or awakening)
• Type II a - caused by server disturbance in arousal. Even if the bladder is full there is no EEG
response and enuresis occurs without any indication of arousal.
• Type II b – due to a latent neurogenic bladder disorder that is only manifested during sleep.
Uninhibited bladder contractions are evident on the cystometrogram when the subject is asleep (but not
on awakening) and enuresis occurs without EEG response.

Physiology of bladder control

1. Detrusor muscle – smooth – involuntary –3 layers
2. Internal sphincter – continuation of the detrusor muscle – parasympathetic - involuntary - S 2,3,4
3. External sphincter – part of the urogenital diaphragm – pudendal nerve – voluntary – S 2,3,4
4. Sensory – stretch receptors – parasympathetic

NOCTURNAL ENURESIS :
Etiology:
Primary –
1. Familial – genetic predisposition
2. Deep sleep – bladder distension either fails to cause central arousal or despite central arousal there is
no awakening or inhibition of micturition (Type 1 or Type II a nocturnal enuresis)
3. Disturbed circadian rhythm of ADH (Vasopressin) secretion – low nocturnal secretion resulting in
higher nocturnal urine volumes. It is suggested that Vasopressin regulated water transport may be
effected through its influence on the expression of aquaporin AQP2 – on the collecting duct (VP

62
 increases AQP2). Aquaporins are proteins that mediate transmembrane water transport in a variety of
tissues including the kidney. ( Scand J Urol Nephrol Vol 31, 1997 suppl 183 page31 - ?32)
4. Small bladder capacity (normal = 30cc/year of age)
5. Structural urological abnormalities e.g.
Neurogenic bladder
Obstructive uropathy with overflow incontinence
Ectopic ureter
Incontinence here is usually diurnal as well as nocturnal
6 Mental retardation
7 Developmental delay in bladder training

Secondary – Non organic more frequent than organic – but must exclude organic first as potentially
serious implications if an underlying pathological organic cause is missed

Organic (1-2%)
1. Renal – urinary tract infection (commonest cause of secondary organic enuresis)
- urinary concentrating defect – e.g. chronic renal failure, nephrogenic diabetes insipidus
2. Endocrine – Diabetes mellitus / Diabetes insipidus
3. Nocturnal epilepsy
4. Dysfunctional voiding - important contribution of constipation

Non organic (>90%)

Emotional / Psychological - Stress/ anxiety- examinations, new school or new sibling

History
1. Symptoms of UTI, developmental delay, polyuria, polydypsia, constipation.
1. Timing of enuresis (diurnal + nocturnal or nocturnal alone).
2. Identify emotions stress /social problems
3. Emotional disorders and encopresis
4. Age of toilet training and nocturnal continence in child and parents.
5. Parent and child reaction to problem
6. Punitive measures
7. Previously tried strategies
8. Drugs –e.g. diuretics
Interview parent and child together and separately

DANGER SIGNS SUGGESTIVE OF ORGANIC PATHOLOGY

1. Diurnal and nocturnal incontinence – suggests neurogenic bladder
2. Continuous dribbling of urine – suggests neurogenic bladder or obstructive uropathy with overflow
3. Poor urinary stream in boys –suggests obstructive uropathy
4. Dysuria – pain or straining at micturition – suggests obstructive uropathy, UTI
5. Passing urine frequently with pain, and in small volumes, offensive urine, gross haematuria –UTI
6. Polydipsia and polyuria – diabetes mellitus or insipidus
7. Abnormalities of the lower back – sacral dimple or sacral tuft of hair- suggests spinal cord anomaly
8. Failure to thrive

Any child with any of the above features should be referred for medical evaluation immediately
A child, on the other hand, who has never been dry and has no danger signs, is most likely to have primary
nocturnal enuresis and the parent/ guardian may try preliminary measures before seeking medical attention.

Examination
Growth parameters, BP, hydration, abdominal examination – renal masses, bladder, fecal masses, perineum
– ectopic ureter / urethral orifices, anal tone, reflexes and power in the lower limbs, lumbo-sacral area for
dimples, sinuses. Observe the urinary stream.

63
Investigations
Urine sediment – centrifuged - for rbc, casts, casts
- uncentrifuged - for bacteria.
Midstream urine – culture and sensitivity
Urine disptix – blood and protein, sugar
Random urine specific gravity (SG) > 1.012 rules out diabetes insipidus and chronic renal disease ( if
proteinuria absent.
Hb, Hb electrophoresis, urea, creatinine electrolytes, bicarbonate.
If urine SG 1.010 – repeat on fasting sample
If SG < 1.005 evaluate for diabetes insipidus (Water deprivation test)

FURTHER INVESTIGATION ONLY IF ABNORMALITY DETECTED ON PHYSICAL

EXAMINATION OR SCREENING TESTS. Most cases of enuresis are nonorganic in etiology.
• Continuous enuresis is always pathological and should be investigated.
• If diurnal and nocturnal enuresis coexist, treat diurnal enuresis first

Treatment of nocturnal enuresis starts seriously at age 5 years or older

1. Treat organic lesion if present – if absent , proceed to (2)
2. Counseling of child to identify stresses, allay anxieties; counsel parent to reward dry nights and cease
punishment
3. Behaviour modification – colour in dry nights with crayon on standard calendar and bring to clinic (or
use sticker – star chart)
4. Withhold fluids at least 2 hours before retiring to bed. Encourage increased daytime fluid intake to aid
bladder stretching
5. Child urinates twice in a row, just before going to sleep, and is awakened by the adult to pass urine one
hour before the predictable enuretic time. (Awaken only once per night)
6. Protect the mattress with a plastic cover and the sheet with a thick towel
7. Do not put the older child in plastic pants as this acts as another means of eroding self confidence
8. The child should help to wash urine out of his wet underwear should an accident occur

9. Bladder exercises (Children > 6 years of age)

- Stream interruption exercises; delay micturition as long as possible and interrupt the stream for as
long as possible before completing the void. Aim is to increase external sphincter tone and
awareness
- Bladder augmenting exercises: Bladder capacity is increased by augmenting diurnal fluid intake
while postponing micturition for as long as possible

10 Enuresis alarms –designed to alert the child or parent when the child wets the bed during the night.
There are many variations in the design of the alarm, from the bulky bed pad and bell, to smaller
devices in the underwear to detect wetness with an alarm on the wrist or attached to the clothes, or
more recently an oscillator in the underwear that vibrates when the underwear becomes wet.
(Evaluation of nine different types of enuresis alarms Arc Dis Child 1984; 59:748-758). If nocturnal
enuresis occurs at a predictable hour, an alarm clock may be set to alarm 1 hour before the predicted
enuresis so the child may be awakened to urinate before enuresis occurs. Alarms should be continued
for 3 weeks after the last dry night and should be a supplement to the other measure (1) – (6).

Results: slow but highest cure rate of all. 80% are dry within 4 months, most within 2 months of
treatment. 10% will relapse.
Mode of action – to awaken child as urine is passed and cause the child to suppress further micturition
voluntarily - thus producing a conditioned response. Enuresis resolves by either nocturia or development
of hypersensitivity to bladder contraction resulting in inhibition of micturition reflex while asleep.

Some predictors of failure include:

• Family stress
• Failure to awaken in response to the alarm

64
 • Abnormal behavioural symptoms
• Lack of parental concern about the problem
• Child’s lack of distress about the enuresis
• More that one wetting episode per night
(Scan J Urol Nephrol Vol 31, 1997, Suppl.183 page 55-58)

11 Drug therapy is a last resort and should only be used in combination with other measures where these
alone have failed. Not recommended for use in children under age 5 years.
Imipramine (Tofranil )
Dose: 10mg orally 1 hour before bedtime. Increase weekly to maximum of 2.5mg/kg/day
Maximum dose: 75mg/day (age 6-12 years)
100mg/day (adolescent)
Duration : initial 2 week trial . Taper to avoid relapse after discontinuation. Give dose on alternate nights
then every third night for 4-6 weeks
Indication : children > 6 years old
MOA –anticholinergic, central action, increases functional bladder capacity
Overdose – cardiac arrhythmia, diastolic hypertension, tachycardia, leukopoenia, hepatitis dermatitis,
insomnia

Desmopressin (DDAVP, Minirin )

Intranasal - 20 –40ug titrated during a period of 4-6 weeks – Initial dose 20 ug
Oral – 200ug/day (maximum 400ug/day). Given ½ hour before or 2 hours after meal as food reduces
absorption

If there was a positive response (substantial reduction in the number of wet nights or a decrease in the
degree of wetness as assessed by the parents) Desmopressin was extended to 3 months using the optimal
dose. If the therapy was still effective after 3 months, treatment was continued for additional 3-6 months
eventually tapering the dose (usually to 10ug, until complete dryness was achieved for a period of 3-6
months). (Scan J Urol Nephrol (1997) 31:Suppl 183, 33-35)

May be ineffective a) in children who do not have derangement of their ADH secretion b) if nose is stuffy

Side effects: dilutional hyponatremia or fluid overload if high fluid intake overnight.

Indications:
a) monosymptomatic nocturnal enuresis (exclusive night- time wetting)
b) b) children > age 5 years

DIURNAL ENURESIS and the NEUROGENIC BLADDER

Definition:
Daytime wetting beyond the age of 5 years – the age at which reliable daytime dryness is expected to have
been achieved.

May be benign or pathological

Relatively benign types
• are characterized by damp underwear only, and no straining
• examples include
1. Urge incontinence – though this may be a symptom of serious bladder dysfunction
2. Stress incontinence – pubertal females, gymnasts on exertion – Treatment: empty bladder before
exertion +/- sympathomimetics
3. Giggle incontinence – sudden complete bladder emptying with giggling only – normal urinalysis
and upper tracts. Treatment: anticholinergics +/- sympathomimetics
4. Transient wetting – UTI, emotional stress, illness – treat cause, reassure

65
 5. Post void dribbling – improper wiping, inadequate shaking (urine trapped under foreskin), vesico-
vaginal reflux (in fat girls with thighs close together urine flows down the perineum to the vagina.
Treatment: void facing the toilet, wipe standing up after voiding.

Pathological forms:
• Frequent voider – uninhibited bladder contractions
• Infrequent voider – large bladder capacity, incomplete bladder emptying, recurrent UTI

General principles of evaluation of diurnal enuresis

• History – assess the severity and frequency of the problem (continuous or intermittent), general health,
social/emotional/ developmental history, constipation, encopresis, symptoms or urinary tract infection.
Dryness for extended periods e.g. at night suggests that there is no serious pathology. Ask about
voiding in a rush (leaving insufficient time for bladder emptying)
• Examination – general – growth parameters, blood pressure, abdominal masses including faecal,
bladder and renal. Specific – perineum for ectopic orifices, lower limb reflexes , spine for defects
• Investigations – screening as for nocturnal enuresis
- where pathology suspected – MCUG, cystometrics, renal ultrasound +/- renal scan

INDICATIONS FOR NEPHROLOGY REFERRAL IN ENURESIS:

• Infrequent voiders
• Straining
• Encopresis or chronic constipation
• Continuous wetness
• Combined diurnal and nocturnal enuresis
• History or examination suggestive of underlying pathology
General management strategies for diurnal enuresis:
• Keep chart – divide day into 4 segments – record and give praise for the dry segments
• Bacteriostatic / fungicidal dusting powder to underwear to reduce the offensive odour
• Bladder training – infrequent voiders: void more frequently – at least every 2 hours – watch alarms
may be used as reminders
- for those who rush micturition: stay on the toilet long enough to void a second time 30
seconds after the first

Pathological diurnal enuresis

PATIENTS WITH NEUROGENIC BLADDERS WILL EITHER FIT THE PATTERN OF THE
INFREQUENT VOIDER (FLACCID NEUROGENIC BLADDER) OR THE FREQUENT VOIDER
(SPASTIC NEUROGENIC BLADDER) AND THE PRINCIPLES OF THEIR TREATMENT ARE
SIMILAR.

Frequent voider
• Types – persistent infantile bladder / detrusor hyper-reflexia
• General features: Urgency, urge incontinence, frequency, staccato stream, squatting (holding postures),
recurrent UTI
• Consequences: potential for bladder wall thickening and VUR
Investigations:
As for nocturnal enuresis

A) Persistent infantile bladder

• Peak incidence 5 – 7 years
• Uninhibited bladder contractions against a contracted external sphincter result in increased intravesical
pressure, bladder wall thickening, trabeculation and VUR in 33 -50%
• Symptoms: urgency, urge incontinence, frequency, staccato voiding +/- nocturnal enuresis,
recurrent UTI, dysuria even after the treatment of UTI, holding postures e.g. Vincent’s curtsey

66
• Ultrasound- small bladder with thickening of the bladder wall and trabeculation
• MCUG -vesico-ureteric reflux (VUR), proximal urethral dilatation due to incomplete relaxation of
external sphincter during voiding
• Urodynamics - detrusor hyperreflexia, reduced bladder capacity, detrusor / sphincter dyssynergia,
increased intravesical pressure, VUR, upper tract damage

B) Detrusor hyperreflexia
• Child attempts to suppress uninhibited bladder contractions during bladder filling by voluntary
contraction of the external sphincter resulting in the characteristic posture
• During bladder filling there may be periodic relaxation of the external sphincter without increase in
the detrusor pressure resulting in a sense of urgency or an episode of urge incontinence
• Bladder emptying is usually complete because normal detrusor contraction and complete external
sphincter relaxation occur at full bladder capacity
• US and MCUG are usually, but there may be mild bladder wall thickening and VUR may occur
• Some children with diurnal enuresis and detrusor hyperreflexia may rarely be unresponsive to
anticholinergics and timed voiding. Some may have spina bifida occulta with associated neurological
abnormalities. Children with diurnal enuresis and spina bifida occulta should have neurological
consultation.
Treatment –
• Anticholinergics to inhibit bladder contractions
• Oxybutynin (Ditropan)
• Hyoscinamide hydrobromide (Levsin)
• Probanthine (Propantheline)
• Terolidine (new drug -very little pediatric experience)
• Treatment and prophylaxis of UTI
• Timed voiding
• Tricyclic antidepressants are ineffective

Infrequent voider: a) Lazy bladder syndrome b) Hinman syndrome

• Voids very 8 –12 hours
• Large capacity bladder
• Incomplete bladder emptying
• Recurrent UTI
• Straining at micturition
• Severe constipation and encopresis

A) Lazy bladder syndrome

• Symptoms of UTI, constipation, encopresis
• Large hypotonic bladder
• Reduced sense of bladder filling ultimately resulting in myogenic failure
• Non obstructive, but because of detrusor hypotonicity straining is needed to empty bladder
• U.S. +/- bladder thickening, mild upper tract dilatation
• MCUG – larger than normal capacity bladder which empties incompletely
• Urodynamics: very large capacity bladder, highly compliant, either unsustained or absent detrusor
contractions, large post void residua, normal relaxation of the external sphincter.
• Management – bladder training, triple voiding, and last resort – intermittent catheterization

B) Hinman syndrome (non neurogenic neurogenic bladder) (pseudoneurogenic bladder), detrusor

sphincter dyssynergia, silent subclinical or occult neurogenic bladder
• Symptoms –urgency, infrequent voiding, weak intermittent stream, severe constipation, diurnal /
nocturnal enuresis, recurrent UTI. Lack of appreciation of bladder filling
• Detrusor / sphincter dyssynergia in neurologically intact children
• Contraction of detrusor against a closed external sphincter results in functional bladder obstruction,

67
 obstructive uropathy, VUR
• US heavily trabeculated, large capacity , poorly compliant bladder, high post void residua, secondary
hydronephrosis, obstructive renal damage
• MCUG: grossly trabeculated, large capacity bladder which empties incompletely, 50% have VUR.
During voiding there is narrowing of the urethra in the region of the external sphincter which fails to
relax and may even tighten, resulting in proximal urethral dilatation, increased intravesical pressure
and weak or intermittent urine stream. There may e seepage of urine despite vigorous contraction of
the external sphincter
• Urodynamics: large capacity , poorly compliant bladder. Uninhibited bladder contractions
• Management –
• Drugs : anticholinergics – for bladder instability, adrenergic blockers (Prasosin –
Minipres) – to inhibit bladder neck contractions, Diazepam, Baclofen – to inhibit striated muscle
hyperactivity
• Bladder retraining and bladder drill (timed voiding every 2-3 hours)
• Intensive correction of constipation –enemas, increased dietary fiber and fluids,+/-
chronic use of fibre based laxatives
• Hypnotherapy biofeedback, psychotherapy
• intermittent catheterization if bladder emptying cannot be otherwise achieved
• surgery for VUR is ineffective as the condition will recur

DIURNAL URINARY FREQUENCY IN CHILDREN

(Polakaluria, neurotic frequency of micturition in children)

• Etiology – unknown ? attention seeking ? reaction to stress

• Sudden diurnal frequency and urgency
• Rarely nocturnal enuresis
• Duration : days to months
• Normal examination, urinalysis and urine culture
• Treatment :
• Identify stress and counsel
• Give more attention
• Timed voiding - delay micturition
• Indomethacin 1mg/kg/dose t.i.d. for 7 days (last resort)
• Is a self limiting disorder

68
 DRUG TREATMENTOF DIURNAL ENURESIS

DRUG DOSE MODE OF ACTION INDICATION

α Sympathomimetics α adrenergic stimulant Giggle incontinence

Increased urethral resistance Stress incontinence
Ephedrine 0.5mg/kg b.i.d (max 1mg/kg Increased bladder storage Do not use if
Pseudoephedrine t.i.d) hypertensive
Phenyl propanolamine 0.4 mg/kg b.i.d (max 0.9mg/kg
Local preparations: t.i.d)
Sudafed syrup: 2.5 mg/kg b.i.d.(max 2.5mg/kg
Pseudephedrine HCL t.i.d.)
60mg/tab, 30mg/5mls
syrup
Anticholinergics Inhibit spasmodic detrusor Giggle incontinence
contractions Persistent infantile
Inhibition of bladder cholinergic bladder
innervation. S/E blurred vision, Detrusor
dry mouth, hyperpyrexia hyperreflexia
Hinman syndrome

Oxybutynin (Ditropan) Starting dose 2.5 mg bid Age > 5 years

Max 5mg t.i.d.

Hyoscyamine (Levsin) 4 doses per day are usually

Tablet 0.125mg effective No age restriction
Elixir 0.125mg/5ml <2years (max 6 doses /day)
Drops 0.125mg/ml wt 3.4kg – 4 drops q4h
Wt 5kg - 5 drops q4h
Wt 7kg - 6 drops q4h
Wt 10kg - 8 drops q4h
Wt 15 kg –11 drops q4h
2 - < 12 years
10 kg ¼ tsp / ¼ tab q4h
20 kg ½ tsp / ½ tab q4h
40 kg ¾ tsp / ¾ tab q4h
50 kg 1 tsp /1 tab q4h
adults > 12 yrs 1-2 tsp / tab q4h

Probantheline 1mg/kg/day (given t.i.d) Age 1 month– 12

(Probanthin) years

αAdrenergic blockers Reduce bladder neck resistance, For incomplete

Smooth muscle relaxants bladder emptying

Prazosin (Minipres) 0.05mg/kg b.i.d.

Max 0.1mg/kg t.i.d

Phenoxybenzamine 0.3mg/kg bid

69
References:
1. Urolog Clin N Am(1995) 75-93 Wetting and functional voiding disorders. Rushton GH
2. Scan J Urol Nephrol (1997) 31:. Suppl 183
3. Pediatr Nephrol (1998) 2: 55-66 Management of the neuropathic bladder of childhood
4. Pediatric Nephrology (1999) 4th Edn. Barratt, Avner, Harmon eds. Lippincott, Williams and Wilkins
pub, page 928

70
 CHAPTER 10

ACUTE RENAL FAILURE

Acute renal failure - Definition

Acute renal dysfunction resulting in azotaemia and disorders of water, electrolyte and acid base
homeostasis.

Definition of oliguria – varies with age

Age Urine output

Neonate < 1 -0.5cc/kg/hr
Infant < 0.6 - 0.8cc/kg/hr (< 15 –20 cc/kg/day)
Child < 0.4 – 0.6 cc/kg/hr (< 10 – 15 cc/kg/day)

Anuria
Urine output less than 1cc/kg/day or no urine passed in the first 48 hours of life.

Aetiology:
Bilateral urinary tract obstruction
Bilateral renal vein thrombosis
Bilateral cortical necrosis
Severe glomerulonephritis

Classification:
Pre-renal – renal hypoperfusion e.g. dehydration, shock
Renal – renal parenchymal disease eg. acute glomerulonephritis, tumour lysis syndrome
Post renal – bilateral obstruction eg. posterior urethral valves

Differentiation of types of acute renal failure

Pre-renal Renal (intrinsic) Post renal

Dehydration Volume overload Palpable bladder or
Clinical Shock kidneys

Fluid challenge + ve - ve (dangerous) - ve

Urine / plasma osmolality > 1.5:1 1:1 variable

Urine specific gravity (USG)* >1.018 1.010 –1.015 variable

>1.015 (neonate)

Urine Na (UNa) mmol/l <10 >25 variable

Blood urea (mmol/l) x 2.8. >10:1** <10:1 >10:1

Serum creatinine (µmol/l)x .01

Microscopy Hyaline and RBC, tubular cells, RBC Normal or WBC /

granular casts haem / granular casts bacteria (UTI)

71
Differentiation of types of acute renal failure ctd.

Pre - renal Renal (Intrinsic) Post renal

Urine: dipstix Negative Positive blood / protein Negative

Renal ultrasound Normal No obstruction Obstruction

Treatment Rehydrate Diagnosis dependent Relief of obstruction

* These values are unhelpful if diuretics are used. Specific gravity may be falsely increased by proteinuria,
glycosuria, mannitol and radio- opaque dyes
** Ratio falsely elevated by blood in GI tract

Therapeutic differentiation of pre-renal from intrinsic renal failure

Severe oliguria / anuria with signs of dehydration

CVP <5-8 mmHg

* Fluid challenge –
N/saline or fresh frozen plasma
(or Blood / albumin depending on clinical situation)
20cc/kg over 1-2 hours or less
repeated until hydration satisfactory
(CVP 10-12 mmHg)

significant response oliguria persists

urine output >2cc/kg/hr

Try Furosemide 2-5mg /kg IV push
Diagnosis: pre –renal failure (dose depends on serum creatinine)
OR
Mannitol *0.5 –1 g/kg IV over several minutes

Treatment : rehydrate
Oliguria Diuresis
Persists
<2cc/kg/hr > 2cc/kg/hr

Intrinsic renal failure Pre-renal renal failure or

Converted oliguric to non
Oliguric renal failure

Note:
• Mannitol* may increase blood volume and cause pulmonary oedema and is not recommended in
congestive heart failure. CVP monitoring of fluid challenge is ideal
• Severe cardiac failure may cause acute renal failure and has the features of pre- renal failure.
The treatment for this type of ARF is improvement of cardiac output and relief of cardiac failure
– NOT A FLUID CHALLENGE!!! Interpret ARF in the clinical setting in which it occurs!
• Dopamine (0.5 –5 µg/kg/min may be used to potentially prevent ARF and improve renal perfusion
after hypoxic / ischaemic renal insults. Higher doses improve cardiac contractility but cause

72
 vasoconstriction and may impair renal function further. (Ped Nephrology 5th edition 1999– pg1125,
Chapter 69- management of acute renal failure)
• Furosemide in high doses may be ototoxic especially in the presence of metabolic acidosis.

Investigatons:
Hb, WBC, platelet count, urea, creatinine, electrolytes, bicarbonate, calcium, phosphate, albumin. Specific
investigations depend on the likely cause eg. glomerulonephritis. Urine (pre-diuretic) – spot urine sodium,
specific gravity, microscopy (spun) for cells and casts. Unspun urine microscopy for bacteria, MSU for
culture, dipstix for blood and protein.

Management:

1. Fluid restriction
Insensible losses (400ml/m2/day or 20-30 ml/ kg/day + output + extra fluid for fever (see Chapter 1)
- may give only insensible losses if very oedematous
- initially if NPO and oliguric, use D10 W only as no electrolytes are necessary and more calories
may be given by this method.
- replace losses as they occur with N/saline (gastric losses) , D5% 0.2Nsaline or D4.3% 0.2 Nsaline
(diarrhoeal losses). Additional Na bicarbonate may be needed in the replacement of diarrhoeal
losses. Use spot urine Na and K to determine Na and K content of urine replacement during the
diuretic phase of ARF. This test is unhelpful if patient has been given a diuretic.

2. Diet and calories

400 kcal/m2/ day – Intravenous D10 W or total parenteral nutrition (Vamin 1.5g/kg/day protein). The
severity of protein restriction (0.5 –1.5 g/kg/day) is dependent on the level of blood urea, the
presence of uremia and the availability of dialysis. No added salt – Na 2mEq /kg/day maximum
(1mEq/kg/day if hypertensive). No sodium IV until diuresing. Early dialysis will permit better
nutrition. Low K if hyperkalemic or normokalemic and oliguric. No K added to IV fluids while
oliguric, unless hypokalemia develops from extrarenal losses.

Phosphate restriction: 500 – 600mg /day (wt <20g) / 600 – 1000mg (wt > 20kg)

3. Metabolic acidosis (HC03 < 15mEq/l, pH < 7.2) – add NaHCO3 2 mEq/kg /day IV / po. .If > 4 mEq/kg
NaHCO3 /day required to correct acidosis, consider dialysis.

4. Hyponatremia – treatment: fluid restriction.

If Na < 130mEq/l and symptomatic (seizures) – 6% NaCl (1mEq /cc) IV. 6 mEq Na Cl /kg increases
serum Na by 10mEq/l. Prepare for dialysis. 6% NaCl is prepared on request from pharmacy. Serum
Na should not rise by > 10mEq /l /hr.

5. Hyperkalemia
K > 5.5mEq/l – Kayexalate 1gm/kg (po /PR) every 1 –2 hours if necessary in sorbitol or D50 W -
constipation
K > 7 mEq/l :
1) Correct acidosis (may cause tetany if hypocalcemic). For each 0.1 pH is reduced, the serum K
increases by 0.6mEq/l) – Na HCO3 1mEq/kg IV over 10 –30 min
2) Dextrose 0.5g/kg/hr till sugar 14mmol/l (250mg/dl) – shifts K into cells. (Destrostix every
hour)
3) ECG changes – tall peaked T waves, wide QRS, prolonged PR interval , flattened P and R
waves, ST depression and prolonged QT interval – Rx 10% Calcium gluconate 0.5ml/kg over
3-5 minutes reverses ECG changes (used with (1) -(3) plus kayexalate.
4) Avoid insulin. If used, dose = 1 unit soluble insulin / 5g glucose given. (0.1U/kg IV over 30
min)
5) B agonists (albuterol / salbutamol– 5-10 mg nebulizer (adult dose) – stimulates cellular uptake
of K – limited paediatric use (Ped Nephr 15th edtn 1999 page 1126)

73
All measures (1-5) for hyperkalemia must be combined with Kayexalate until either diuresis occurs or
dialysis is instituted, to remove K from body

6. Hypocalcemia - < 2mmol/l. – usually occurs when PO4 > 1.8 mmol/l. If symptomatic Rx 0.5cc/kg
10% calcium gluconate IV over 5 minutes preferable with ECG monitoring. Watch for
bradycardia. Maintain with 120cc/m2/day of 10% calcium gluconate (See also Chapter 1 for
calcium correction in hypoalbuminemia, and Chapter 7)

6) Hyperphosphatemia– reduce dietary PO4, phosphate binders calcium carbonate 220-500mg/kg/day po

7) Seizures

• Rx hypoglycemia : IV 0.5cc/kg D50W diluted in equal volume of water for injection, then
maintain on D10w IV
• Rx s hypertensive crisis (see Chapter13 )
• Rx electrolyte, calcium imbalance
• Diazepen, Dilantin, phenobarbitone
• Prepare for dialysis

8) Hypertension – (see Chapter 13)

Monitor
BP , pulse, RR frequently
Daiy weights, accurate intake and output
Urine electrolytes – Na and K aid in determining replacement fluid (pre – diuretic)
Electrolytes, calcium phosphate, urea, creatinine, (+/- glucose) at least daily

NOTE:
• Once urine output in the diuretic phase has been constant on regime of insensible losses and output,
gradually reduce intake and allow urine concentration to occur
• On dialysis:
• Allow sufficient fluid intake to cover dialysis losses and give adequate calories, while
ensuring net fluid removal if still fluid overloaded
• Monitor blood glucose – hyperglycemia may occur
• Daily peritoneal fluid samples for gram stain cell count and culture to detect peritonitis early
• Dialysis losses may be adjusted to enable sufficient fluids for adequate caloric intake to be
given

Tumour lysis syndrome:

• Noted in patients with high tumour loads or B cell neoplasms.
• Associated with elevated serum uric acid and serum phosphate, hyperkalemia and hypocalcemia
• Uric acid deposition in the tubules results in intrinsic renal failure
• Rx: alkalinization of the urine (pH > 7), Xanthine oxidase inhibitors (eg Allopurinol), slow
introduction of chemotherapy. Some patients may need dialysis.
Ref. Pediatric Nephrology (1999) 13: 153-162.Renal involvement in children with malignancies

74
 Drug dose adjustments for children in renal failure

Use of the table:

1) Determine your patients actual DFR in ml/min/1.73m2 as follows:

GFR (ml/min/1.73m2 = Ht (cm ) x K

Serum creatinine (µmol/l) X 0.01

K= 0.55 (age 2-12 years)

= 0.33 (low birth weight infants <1 year)
= 0.45 (full term infants < 1 year)

2) Convert GFR (ml/min) on table to ml/in/1.73m2 as follows:

GFR ml/min/1.73m2 = GFR ml/min x 1.73
BSA (m2)
BSA = your patient’s body surface area
3) Compare GFR ml/min/1.73 m2 on Table (2) with your patients actual GFR and determine into which
category your patient falls
eg. a child has a GFR calculated as in (1) of 60ml/min/1.73m2. Her BSA is 1m2.
Therefore, from Table, GFR of 50ml/min = 50 x 1.73 = 86ml/min/1.73 m2
1
and a GFR of 10ml/min = 10 x 1.73 = 17ml/min/1.73 m2

So for drug dose adjustment, she would fall into the category GFR 10 – 50 ml/min

Abbreviations: (R ) renal
(H) hepatic
(D) dosage
(I ) interval

Adjustments may be made to either the dosage (D ) or dosing interval ( I ) or both (see
Method on Table). The numbers given for dosage are the % of normal daily dose, and for
interval, represents the hours between doses.

75
 Drug adjustments:
Elimination Method of GFR GFR GFR Comments
Drug And adjustment (mls/min) (mls/min) (mls /min)
metabolism >50 10 - 50 < 10

Aminoglycosides
Amikacin R D 60-90 30-70 20-30 Ototoxic and nephrotoxic;
need usual loading dose
I Every Every Every in renal failure. Need ½
12-18 12 24 to 2/3loading dose after
haemodialysis

Gentamycin, R D 60-90 30-70 20-30

Kanamamycin I 8-12 12 24
Tobramycin

Neomycin R I No change 8-12 12-36

Antifungals
Nephrotoxic: renal
Amphotericin B NR I 24 24 24-36 tubular acidosis;
hypokalaemia:
nephrogenic DI

Flucytosine R I 6 12-24 24-48 Hepatic dysfunction :

Marrow suppression

Ketoconazole H D None None None

Antivirals
Acyclovir R I 8 24 48
Cephalosporins Cephalosporins:
Cefaclor R (H) D 100 50 -100 33 May be nephrotoxic in,
combination with
Cefadroxil R I 8 12-24 24-48 aminoglycoside
antibiotics,
diuretics and volume
Cefazolin R I 8 12-24 24-48 depletion.. Rare

Cefotaxime R (H) I 6-8 8-12 12-24 allergic interstitial

Cefuroxime R I 6-8 8-12 12-24 nephritis Absorbed well

Cephalexin R I 6 6-8 12 from peritonea fluid in

CAPD; Transfer from
Cephalothin R (H) I 6 6 8-12

Ceftazidime R D None None 50 blood to peritoneum is

I 12 12 24 poor
Ceftriaxone
R/H none none none none

76
Drug Elimination Method GFR GFR GFR Comments
And Of (mls/min) (mls/min) (mls/min)
metabolism Adjustment
Meropenem D/I - (26-50 ) Give unit dose at end of
R 1 unit dose q ½ unit dose haemodialysis
12 h q 24 h
(10-25)
½ unit dose q
12h

Chloramphenicol H (R) D none none none

Clindamycin H D none none none

Erythromycin H D none none none

Lincomycin H (R ) I 6 12 24
Vestibular toxickty: GI
symptoms like uraemia
Metronidazole H (R ) I 8 8-12 12-24
H (R ) D 100 avoid avoid Metabolits accumulate
Nalidixic acid Met acidosis in overdose
NR (R ) D 100 avoid avoid Peripheral sensory
Nitrofuranoin neuropathy: ineffective
when GFR <30ml/min

Penicillins: Interstitial nephritis,

seizures / coagulopathy

(> 30 (10-30ml/min)
R(H ) I ml/min) 12 24
Amoxil 8 (max 500mg (max 500mg
bd) od)

Ampicillin R(H ) I 6 6-12 12-16 3mmol Na /g

(> (10 – 30 In adults GFR 10-

30ml/.min) ml/min) 30ml/mim0 1.2g IV load
Augmentin R(H) I then 600mg bd
12 24 GFR<10ml/min- 1.2gIV
8 load then 600mg od
R(H ) D none none none

Cloxacillin
K salt has
R(H) I 6-8 8-12 12-16 1.7mmol/million units
Penicillin G

Sulphonamides +
Trimethoprim (TMP)
TMP / Protein binding decreased
Sulphamethoxazole H(R) I 12 18 24 in uraemia

77
Drug Elimination Method GFR GFR GFR Comments
And Of (mls/min) (mls/min) (mls/min)
metabolism Adjustment

Trimethoprim R(H ) I 6 8-12 12-24

Vancomycin R I 24 -72 72 - 240 240

Elimination Method GFR GFR GFR

Drug and of mls/min mls/min mls /min Comments
metabolism adjustment > 50 10- 50 < 10

Analagesics

Paracetamol H I 4 6 8 Nephrotoxic in overdoses

H (R) I 4 4-6 Avoid Nephrotoxic in
Acetyl salicylic acid overdoses; may decrease
(Aspirin) GFR when RBF is
prostaglandin dependent;
excretion enhanced in
alkaline urine; may add to
uraemic gastrointestinal
and haematological
symptoms

Opiates: All these may cause

Codeine, morphine, excessive sedation and
naloxone, pentazocine H D none none none respiratory depression

Almay cause excessive

Benzodiazepines H D none none none sedation and
encephalopathy in
patients with ESRD

Chloral hydrate H D none avoid avoid May cause excessive

sedation

Phenothiazines -
Chlorpromazine H D none none none

Antihypertensives BP is best guide to dose

and interval

Prazosin H (R ) D none none none

Significant accumulation
Atenolol R D none 50 25 in ESRD
Hypotensive effect may
Metoprolol H D none none none last 24 hours

Propranolol H D none none none

78
Drug Elimination Method GFR GFR GFR Comments
and Of (mls/min) (mls/min) (mls/min)
metabolism Adjustment

Labetalol H D none none none

Elimination Method GFR GFR GFR

Drug and
metabolism mls/min mls /min mls/min
> 50 10 -50 < 10

Captopril R(H ) D none none 25

(<80 >30) (< 30 > 10) (< 10) Adult guidelines only
Enalapril I or D D 5 –10 mg D 2.5 – 5 mg mg (dialysis
days)

(GFR 50 – 20 GFR < 20ml

Rimipril D none ml/min/1.73m2 /min/1.73m2 )
)
1.25mg-5mg avoid
24

Diazoxide R (H) D none none none

I 8 8 8-16
Hydrallazine H (NR ) 12-24

Minoxidil H D none none none

Nitroprusside NR D none none none

Non renal excreted-no

Calcium blockers dose adjustment needed

D H none none None

Nifedipine

Digoxin R D 100 25-75 10-25

I 24 36 48

Diuretics

Furosemide R (H) D none none none ototoxic

Spironolactone R I 6-12 12-24 avoid

R none none avoid Ineffective when GFR <
30ml/min

Thiazides

79
Drug Elimination Method GFR GFR GFR Comments
And Of (mls/min) (mls/min) (mls/min)
metabolism Adjustment
May potentiate uraemic
Anticoagulants bleeding

Heparin NR D none none none

Warfarin H D none none None
Anticonvulsants
Phenytoin H ( R) D none none none Interstitial nephritis.
Sodium valproate H D none none none

Carbemazepine H D none none none Possible SIADH

Drug Elimination Method GFR GFR GFR Comments
And ml/min Ml/min Ml/min
metabolism >50 10 - 50 <10
Anti-inflammatory
drugs

Allopurinol R D none 75 50
I 8 8-12 12 - 24

Indomethacin H(R <15%) D none none none

Antineoplastic agents

Azathioprine H D none none none Allopurinol increases

24 24 36 drug effect

Cis platinum R D none 75 50 Nephrotoxic.

Cyclophosphamide H D None None 50-75

I 12 12 18-24
Acute renal failure and
Doxorubicin H (R ) D none none 75 nephrotic syndrome
Nephrotoxicity prevented
Methotrexate R D none 50 avoid by urinary alkalination,
forced diuresis
Nephrotoxicity, acute
Mithramycin R D none 75 50 renal failure, decreased
Ca++, K+, PO4-

Mitomycin C R D none 75 50 Nephrotoxicity

Vinblastine H D none none none

Vincristine H D none none none

Corticosteroids H D none none none May aggravate azotaemia,

Na retention

D 100 75 50
Cimetidine R I 6 8 12

80
References re Drug doses:
1. Paediatric Nephrology (1997) 1: 183 – 194 (for drug dose adjustments)
2. Package inserts of various drugs

Bleeding in Uraemia
Etiology:
1. Inhibition of platelet function by uraemic toxins
2. Reduced function of Von Willebrandt’s Factor (vWF)
3. Increased nitric oxide (NO) production resulting in platelet dysfunction. Blocking nitrous oxide
production in uremic anaemia corrects bleeding time
4. Increased half life of heparin in uremic patients may result in prolongation of PTT after dialysis
5. Anaemia may increase the risk of bleeding:
• In anaemia, the blood flow is less turbulent, and the platelets have less chance to interact with the
damaged vasculature
• RBC’s contain enzymes which augment platelet function

Assessment of platelet function: - clinical:

1. Platelet number
2. Bleeding time vs platelet closure time:
• The bleeding time in some patients bears no relationship to the platelet count.
• The bleeding time is not a specific indicator of platelet function
• The bleeding time is a poor indicator of surgical risk
3. The platelet closure time is sensitive to platelet adherence and aggregation abnormalities and therefore
has increased sensitivity for vWF screening compared to the bleeding time.

Treatment of acute uraemic bleeding:

1. DDAVP or
2. Cryoprecipitate or
3. Estrogens
4. Vascular factor
5. Nitric oxide synthesis inhibitors
6. Epogen / blood transfusions
7. Dialysis
8. Adjunctive treatment – transfuse to PCV of 30% (to overcome negative effect of anaemia) +/- platelet
transfusion

Drugs:

Cryoprecipitate: (Cryoprecipitate contains Factor VII, vWF, fibrinogen and factor III, and virtually all
plasma components.

• Mode of action in uremic bleeding unknown

• Reduces bleeding time for 1 – 18 hours
• It will not reduce the bleeding time in all patients
• Dose 2 units / 10 kg will increase the fibrinogen level 100mg/dl except in DIC
• Usual dose given is 10 units IV q 12 hours (adult)
• Used in uremia if patient unresponsive to other modalities eg dialysis , DDAVP or oestrogen
• Risk transmission of blood borne diseases

DDAVP:

81
Mode of action
• Stimulates vWF release from the endothelial cells
• Improves ATP release
• Increases serotonin uptake
• Increases serotonin uptake
• Increases catecholamine release

DDAVP Dose:
• 0.3ug /kg IV or subcutaneously. IV dose given in 100 cc Normal saline over 45 minutes
• 3.0umg /kg intranasally
• onset of effect in 1 hour
• duration 4 – 24 hours
• Tachyphylaxis begins at 24 – 48 hours

Indications
• For short term prevention of uremic bleeding

Dialysis
• Partly corrects bleeding time -- Causes slight increase in vWF
• Increases protein C

References for cryoprecipitate

• Guidelines for the administration of cryoprecipitate – The Wadsworth Center- New York State
Department – New York State Council on Blood Transfusion Services – January 1995 – Revised
January 1996)

82
 CHAPTER 11

ACUTE PERITONEAL DIALYSIS

Indications in acute renal failure

Absolute:
1) Severe fluid overload with CCF
2) Severe hyperkalemia unresponsive to medical Rx or with ECG changes
3) Severe hyponeatrmia
4) Server metabloic acidosis requiring > 2 doses of NaHCO3 (2mEq/kg/dose)
5) Uraemia
6) Fluid restriction curtailling ample nutrition

Relative:
1) Anuria
2) High urea and creatinine values alone are not indications

METHOD

Materials:
1) Pertioneal dialysis tubing, trocar and cannula
2) Yellow intracath #14 gauge needle – 12 –24 inches long
3) Cut sown set with narrow blade
4) 2/0 silk on a straight needle
5) peritoneal dialysis fluid 1.5% dianeal (warm the fluid by placing in container of warm water
6) Lignocaine, Iodine, alcohol, mask and sterile gloves

Method: A
1) Consent form to be signed
2) Cross match 1 unit blood
3) Check PT, PTT platelets beforehand
4) Insert urethral catheter to empty bladder
5) Cleanse abdomen with Iodine and alcohol
6) Set up dialysis bags and attach to tubing (fluid should be tepid– not hot and not cold)
7) Determine, before dialysis starts, the volume to be run in and mark out on bag (See Figure 1).
The markings are not exactly in the same position on all bags, so this method is only an
approximation. If more accurate measurement is needed, a Biuretrol must be attached to the
dialysis bag
8) Fill tubing with fluid
9) If the abdomen is not tense with ascites, by infusing dialysis fluid until adequate tension is
present one reduces the risk of damaging internal structures eg aorta, inferior vena cava and
bowel. Proceed to step B
10) If the abdomen is already tense with ascites, proceed to step C

83
 Figure 1 – Dialysis bags and volume markings

B
The procedure is as follows:
1) Remove guide wired from intracath
2) Set up tubing to dialysis fluid
3) Local anaesthetic to skin – superficial and deep at area of proposed intracath insertion
Direct the needle of the intracath downwards gently but firmly
When you feel the “pop” thread the tubing and withdraw the needle around it
Push tubing in as far as it will go – do not press deeply with the needle
4) Run in 30-50 cc/kg of dialysis fluid – sufficient to make abdomen tense
5) Withdraw intracath
6) Proceed to insertion of peritoneal dialysis catheter

C
Insertion of the peritoneal dialysis cannula:
1) Site of catheter – approximately 2 -3 cm inferior to the umbilicus and in the midline
2) Make a small incision at this point with the pointed end of the blade to include skin and subcutaneous
tissues – just big enough for catheter

84
3) Hold peritoneal dialysis catheter – with pointed trocar inside. Hand on top of catheter pushing
downwards firmly
4) When you feel the catheter enter the peritoneal cavity (a pop), remove the trocar (pointed internal
metal rod) and thread cannula (plastic part around the trocar) into peritoneal cavity quickly aiming the
cannula to the right or left iliac fossa (R preferably). Push in as far as it will go
5) Connect cannula (dialysis catheter ) to “elbow” and thus the remainder of tubing (already primed with
fluid)
6) Run out fluid from cavity into tubing – should run as a steady stream
7) Pour in expected exchange volume
a) 40-60cc/kg infants and small children
b) 30-40cc/kg older children

Limiting factors – abdominal discomfort, peritoneal leaks

8) If fluid runs in and out quickly after 3 rapid exchanges – without dwells – put purse string suture
around cannula – tie tightly, fasten securely at the level of the skin then tie 3-4 knots up the side of the
catheter with the same uncut suture

DIALYSIS

Cycles: Usually best clearance with 30 minute cycles :

• In over 5 minutes
• Dwell over 20 minutes
• Drain over 5 minutes
• Tepid fluid

Clearance: Urea > K > Cl > Na > Cr > PO4 > uric acid > HCO3 > Ca > Mg

Dianeal composition: Na 132 K 0 Ca 3.25 Mg 1.3 Cl 101.75 Lactate 35 mmol/l

Rate of water removal (assuming adequate drainage) depends on [glucose] in dialysis fluid

• 1.5% dianeal (1.5% glucose) usually adequate, but may increase to 2.5% or 4.25% if inadequat fluid
removal. If there is no pre-mixed 2.5 % or 4.25% dianeal, they can be prepared as follows
• to make 2.5% from 1.5% - add 40cc of D 50 W / 2 liters of fluid of 1.5% dianeal
• to make 4.25% from 1.5% - remove 110 cc fluid from 2 litre bag of 1.55 dianeal. Add 110 cc of
D50W to bag

ADDITIVES

1) KCl 6 mEq / 2 liters added when serum K <4.0mEq/l

- may be increased in increments of 2-4 mEq/2l bag depending on serum K
2) No antibiotics prophylatically
3) Heparin 1000 units /2 litres of dialysis fluid in all bags to minimize formation of fibrin strands

PERITONITIS

Initial broad spectrum cover for peritonitis.

85
Empiric therapies:
Intraperitoneal –
1) Cloxacillin 200mg/ 2litres + Gentamycin 10 mg /2 litres (regime used at UHWI with success despite
potential for inactivation when aminoglycosides mixed with penicillins) – Staph is commonest
pathogen for peritonitis here
2) Cefotaxime - 500mg/2 litres
Adjust when sensitivities available

Loading dose of antibiotics in treatment of peritonitis:

First Line Drugs Loading Dose (per 2litres dialysate)

Cloxacillin no loading
Gentamycin 16 mg/2l
Cefalothin / Cefotaxime Cefalothin 500mg cefotaxime1g
Tobramycin / Gentamycin 16mg Tobramycin and Gentamycin

Second Line Drugs Loading dose (per 2 litres dialysate)

Ampicillin no loading
Amoxicillin 500 – 1 g
Ticarcillin 2g
Trimethoprim/sufamethoxazole 640 mg /3200 mg
Clindamycin 600mg
Amikacin 50 mg
Penicillin 2MU
Vancomycin 1gm/2l
Amphotericin B 1mg /kg IV
Cefuroxime 400 mg
Ceftazidime 500 mg
Fluconazole no load
Flucytosinnne 50 mg /kg IV/ po (max dose 2.0gm)

Recommended maintenance doses of intraperitoneal antibiotics for treatment of peritonitis (per 2litres)
Penicillin 100,000 U
Ampicillin 250mg
Amoxicillin 100 mg
Cloxacillin 250 mg
Ticarcillin 200 mg
Cephalothin / Cefotaxime Cephalothin 250 mg / Cefotaxime 500 mg
Ceftazidime 250 mg
Cefuroxime 250 mg
Vancomycin 60 mg
Tobramycin 8 mg
Amikacin 24 mg
Gentamycin 8 mg
Clindamycin 300 mg
Trimethoprim / sulphamethoxazole 160 / 800
5 Fluruocytosine Flucytosine 25 – 37.5 mg /kg po q 24 hr (max 1g)
Amphotericin B 1mg /kg/day IV
Fluconazole 3- 6 mg /kg IP / IV or PO q 24 – 48 hours (max dose 200mg)*
Rifampin 20 mg / kg /day po (max 600mg /day)
Taken from “ Consensus guidelines for the treatment of peritonitis in pediatric patients receiving
peritoneal dialysis” – Peritoneal Dialysis International Vol. 20: 610 – 624

86
PRECAUTIONS
• Daily peritoneal fluid: c/s, gram stain, cell count. > 100 WBC / ml and > 50% neutrophils suggests
peritonits. – start Rx as soon as sample taken for culture. Fluid is aspirated from the porthole (rubber
bung in tube in the dialysis line near patient entry) with a 25 gauge needle attached to a sterile syringe.
Clean the porthole with Iodine and wrap with Iodine soaked gauze for 10 minutes prior to inserting the
needle, in order to avoid iatrogenic peritonitis.*
• Nurse is asked to call if problems arise (see below)

PROBLEM SOLUTION

• Dialysis fluid running slowly out or fluid

retained on > consecutive cycles
• change patient’s position
• change catheter position
• Flush with heparinized saline 1000 units / 10
cc N / saline at porthole nearest Catheter entry
(use 25gauge needle and clean the porthole as
above prior to needle insertion*.)
• Run fluid in – no dwell, then out
• Increase the drain time
• Change the catheter

• Dialysis fluid running in slowly Flush catheter as above

• Bloody dialysate or fluid leaking around the Put 2nd tighter row of purse string sutures around the
catheter catheter + ensure that heparin 1000u /2 litres has
been added to the bag (should be added from the
initiation of dialysis normally)

• Dialysis fluid cloudy • Peritonitis – fluid for cell count, gram stain and
culture
• Start empirical antibiotics (Clox and Gent) –
see peritonitis – adjust when culture and
sensitivities available
• Abdominal pain • Dialysis fluid too hot – drain and replace with
TEPID SOLUTION
• Change catheter position

• Fever Screen for infection

• Too much fluid being removed per exchange • Reduce glucose concentration of dialysis fluid
• Replace excess losses IV / po

• Inadequate fluid being removed per exchange Increase glucose content of dialysis fluid –
1.5% / 2.5 % / 4.25 % (see C)

Change PD catheter if unable to get good drainage or inflow despite the above measures. Always flush the
tubing with about 20 –50 cc of fluid as catheter is being withdrawn to minimize possibility of omentum
coming up in the catheter as it is being removed. Discontinue dialysis when urine output has improved
sufficiently that the original indications for dialysis are unlikely to recur off dialysis (not just when the lab
results are normal on dialysis).

87
References:
1) ISPD guidelines / recommendations. Consensus guidelines for the treatment of peritonitis in pediatric
patients receiving peritoneal dialysis. Warady, Schaefer et al. Peritoneal Dialysis International 2000.
20:610 – 624.
2) Paediatric Nephrology (1997) 1: 183 – 194 (for drug dose adjustments)
3) Pediatric Nephrology 15th Edition (1999) Barratt and Vernier Chapter 69 (1125 – 1126)

88
 CHAPTER 12

CHRONIC RENAL FAILURE (CRF)

Definitions:
• Renal impairment: glomerular filtration rate (GFR) 50-80% of normal for age*
• Chronic renal insufficiency: GFR 50 -25% of normal for age* - growth failure, impaired calcium
absorption, abnormalities in plasma constituents
• Chronic renal failure: GFR < 25% of normal for age* for at least 3 months- associated with
osteodystrophy, anaemia, hypertension and sometimes uraemia
• End stage renal failure (ESRF): GFR <5% of normal for age*- insufficient to support life without
renal replacement therapy- symptoms: lethargy, somnolence, anorexia, nausea, vomiting, coma and
eventually death
*For age related normal values see Assessment of Renal Function

Aetiology
• Congenital - e.g. Dysplasia, polycystic kidneys, obstructive uropathy, reflux nephropathy
• Acquired - e.g. glomerulonephritis, tubulointerstitial disease, vascular pathology, chronic acquired
obstructive uropathy, tumours

Investigations
1. Blood urea, creatinine, electrolytes, serum albumin, Hb, reticulocytes, film, Hb electrophoresis, serum
ferritin or serum iron and TIBC (measure iron stores)
2. Serum calcium (reduced), phosphate (increased), alkaline phosphatase (increased) - osteodystrophy
3. Serum bicarbonate (reduced), serum uric acid (increased)
4. +/- fasting cholesterol and triglycerides
5. Spot urine: protein, phosphate and creatinine, sodium (for salt wasters)
6. Estimate GFR using Schwartz formula (see Assessment of Renal Function)
7. Estimate degree of proteinuria by spot urine (see Assessment of Renal Function)
8. 24 hour urine or timed urine to quantitate 24 hour urine volume
9. Calculate tubular reabsorption of phosphate (TRP) as index of PTH activity (or measure PTH levels).
Ideal sample: fasting urine phosphate and creatinine with fasting serum phosphate and creatinine
TRP = 1- [urine/ plasma phosphate**] X 100%
[urine / plasma creatinine***]
** units mmol/l ***units umol/l

Normal > 80% Hyperparathyroidism <80%

10. Radiology
• Renal ultrasound (renal lengths) and appearance - kidneys <2SD below mean for age suggest
chronic rather than acute renal disease
• Renal glucoheptonate scan for scarring, perfusion and function - if reflux nephropathy / chronic
pyelonephritis thought to be the cause
• DTPA renal scan for perfusion and function. In other centres a GFR scan can be obtained from
this study. The machine at UHWI cannot perform GFR scans on children < 18 years of age
• For renal osteodystrophy (Renal osteodystrophy series) - non dominant hand
a) L wrist - bone age and evidence of metaphyseal rachitic changes
b) L hand - penetrated view - for subperiosteal resorption of terminal
phalanges in hyperparathyroidism
• Micturating cystogram for vesico-ureteric reflux and outflow obstruction - lower tract
visualization is eventually needed in all children being considered for transplantation - may have
to be performed early in the case of children with suspected obstructive uropathy / reflux
nephropathy vs later in those with glomerular disease

• CXR / ECG if hypertensive

89
11. Renal biopsy - Contraindicated if kidneys shrunken - i.e. end stage kidneys - high risk of
haemorrhage and histology unlikely to be helpful

Monitoring

1. Growth parameters, BP, urinalysis - each visit

2. Frequent urine cultures in children whose pathology is obstructive uropathy / reflux nephropathy
especially those with neurogenic bladders on intermittent catheterization. (See Urinary Tract Infection)
3. Blood:
• Hb, urea, creatinine, electrolytes, serum proteins, calcium, phosphate and alkaline phosphatase - at
least every 3 months - correct the derangements observed eg metabolic acidosis and hyperkalemia.
• Iron studies as indicated
• Fasting cholesterol and triglyceride once per year
4. Urine: spot urine phosphate and creatinine - monitor TRP to follow adequacy of osteodystrophy
therapy (at least every 3 months)
5. Estimate GFR regularly using Schwartz formula, plot 1/serum creatinine vs time to assess the
progression of renal failure, and predict the time of end stage disease
6. Renal osteodystrophy series every 6 months once TRP is normal - bone age yearly
7. Remember to check tables for drug dosage adjustments for renal failure especially when
prescribing antibiotics

Management

Diet
1. Protein :
• restricted to RDA+ (recommended dietary allowance) only when GRF < 50% of normal for
age
• should contain essential amino acids and proteins of high biological value
2. Calories:
• 100% of the RDA for height age
• weight for height is reduced or if there is other evidence of malnutrition, increase calories to
120% of RDA +
• 75% carbohydrate 20% fat and 5% protein (concern re diets high in fat because
hyperlipidemia common in CRF, and also high carbohydrate diets which may contribute to
hyperinsulinemia and subsequent hypertriglyceridemia)
• infants may use supplements of polyunsaturated corn oil or medium chain triglycerides (MCT
oil)
3. Phosphate:
• Limited to the RDA+
• Aim to keep serum phosphate level normal for age (see Assessment of Renal Function)
• Phosphate binders should be given immediately after mealtime to enhance dietary phosphate
binding
• Calcium carbonate and acetate are the preferred phosphate binders
• Aluminum containing phosphate binders are not recommended, but for patients who cannot
afford to by the calcium products they may have to be used- risk of Al toxicity - osteomalacia,
microcytic anaemia, encephalopathy
4. Sodium:
• Restricted to 1mEq/kg/day if oedematous or hypertensive
• Otherwise 2mEq/kg/day.
• Small infants and older children with tubular disease may waste sodium and may demonstrate
poor weight gain until salt supplementation of 2 - 15 mEq/kg/day is added

5. Potassium:
• Restriction is usually necessary when GFR <5 ml/min/1.73m2 (end stage disease)

90
 • In potassium wasting tubular disorders additional K may be needed

6. Fluids:
• In CRF of glomerular aetiology, fluid restriction is usually needed early in the illness
• In CRF of tubular aetiology, polyuria is usual, and high fluid intakes are needed to prevent
pre- renal failure. However in end stage renal failure from whatever cause, fluid excretion is
impaired and fluid restriction will be needed. Urine volumes in the polyuric patients need to
be measured periodically

Recommended Dietary Allowances+

Adapted from National Academy of Sciences. Recommended dietary Allowances.
10th ed. Washington, DC: National Academy press, 1989

Age Midpoint Weight Energy Energy Protein Protein Calcium Phosphate

Height
Total
(yr) (cm) (kg) Kcal/kg (rounded) g/kg Total (mg) (mg)

0-0.5 60 6 108 650 2.2 13 400 300

0.05 -1.0 71 9 98 850 1.6 14 600 500

1-3 90 13 102 1300 1.2 16 800 800

4-6 112 20 90 1800 1.2 24 800 800

7-10 132 28 70 2000 1.1 31 800 800

11-14M 157 45 55 2500 1.0 45 1200 1200

11-14F 157 46 47 2200 1.0 46 1200 1200

15-18M 176 66 45 3000 0.9 59 1200 1200

15-18F 163 55 38 2200 0.8 44 1200 1200

19-24M 177 72 40 2900 0.8 58 1200 1200

19-24F 164 58 36 2200 0.8 46 1200 1200

Drug therapy

1. Prevention and treatment of bone disease:

• Correct hyperphosphatemia, then start Vitamin D therapy. Vitamin D therapy should be started
once GFR < 50% of normal for age (<50mls/min/1.73m2).
• Monitor serum calcium, phosphate and alkaline phosphatase, TRP and growth. Effective therapy
results in normalizing of serum calcium phosphate and alkaline phosphatase and improvement in
growth.

91
 • Avoid aluminum containing phosphate binders. Do not use these preparations with citrate
containing medications and citrus fruits as they enhance aluminum absorption.
• Calcium carbonate is currently the preferred phosphate binder
• Aim to keep Ca / PO4 product <5.64mmol/l

2. Correction of metabolic acidosis - maintain serum bicarbonate -minimum of 20mmol/l

3. Prevention of folate, vitamin and mineral deficiency
4. Treatment of hypertension
5. Treatment of anaemia:
Erythropoietin (r-HuEPO- recombinant human erythropoietin) - Eprex
• May be given SC (subcutaneously)- usual route, IV (intravenously)- hemodialysis patients, or
intraperitoneally (IP) - patients on peritoneal dialysis
• Dose 150 U/kg/week SC /IV
• If given SC add Lignocaine as injections painful
• Contraindications- uncontrolled hypertension, poorly controlled seizures (seizures within the
preceding 12 months), severe iron deficiency (transferrin saturation <5%), pregnancy,
uncontrolled hyperkalemia
• Start iron supplements at initial dose of 3mg Fe2+ /kg/day orally if serum ferritin <100ng/ml
+/or transferrin saturation < 20%. Adjust dose until values normalize. Iron supplements
should not be given within 2 hours of a meal and not with phosphate binders as absorption is
enhanced by gastric acidity
• Aim for target Hb 10-11g/l or at least 2SD below the mean for age, but
< mean Hb for age
• Monitor weekly-Hb, PCV, Retics, electrolytes, every 2 weeks -serum Fe, TIBC, ferritin,
transferrin, monthly -urea, creatinine, CBC, physical examinations. Daily BP at start of
therapy
• Complications - Hypertension, hyperkalemia, iron deficiency and seizures - withhold
medication if this occurs
• Duration of treatment - till target Hb achieved. Dose increased if target Hb not achieved by 12
weeks and reduced when target achieved
7. Treatment of short stature - with rhGH (recombinant human growth hormone)- not locally available
8. Renal replacement therapy-
• Dialysis -
-peritoneal - CAPD- continuous ambulatory peritoneal dialysis
CCPD - continuous cycling peritoneal dialysis
-hemodialysis
• Renal transplantation

92
 Vitamin D preparations used in CRF

0.015 -0.05ug/kg/day Capsules 0.25ug and 0.5ug.

Rocaltrol (calcitriol)
1,25-dihydroxyvitamin D3
Alphacalcidiol
1α hydroxyvitamin D3
Dihydrotachysterol (hytacherol)
Vitamin D2
(calciferol)
(given bid)- usual maximum GFR < 50% of
0.9ug/day
1.0ug 3x /week nocte
reduce dose to 2 x or once per
week when PTH < 100ng/l or
TRP normal
0.125 –1.5mg od
0.2 - 0.6mg/day
Peak effect in 3 days. t/2 <24
normal hours
" Mixture or capsule
Capsules 0.125mg
" Peak effect 15 days
t/2 50 hours
1.25mg /tablet - only if no
" other Vit D available- peak
effect 30 days- t/2 20days

Other drugs used in CRF -

Drug Usual dose Indication Comment

Calcium carbonate 20-220mg/kg/day -given hyperphosphatemia Usual daily dose 5.1 +/-2.5g
tid immediately after meals Tums 500mg CaCO3/tab

Aluminum hydroxide 10-30mg/kg/day - given tid hyperphosphatemia Avoid if possible - toxic

immediately after meals Aludrox 375mg/tab No citrate
Sodium bicarbonate 2-5mEq/kg/day given tid Serum bicarbonate
<20mEq/l
Folic acid 1-2mg/day (od) Avoid folate deficiency Folic acid tabs 5mg (2.5mg OK)
B vitamins-
(Multivite) Orovite 1 tab od Prevention of B1, B2, B5, NO vitamin A preparations
Beminal liquid 5mls od B6 and biotin deficiency (eg Tropivite ) -risk of toxicity
Becoplex syrup (hypercalcemia)

Vitamin C In multivit preparation Prevention of deficiency Do not use with Al hydroxide

FeSO4 2mg/Kg Fe2+ od Prophylaxis of iron 5mgFeSO4 = 1mg Fe2+

deficiency prescribe in terms of Fe2+content
Kayexalate
(Resonium A) 1-2g/kg/dose Hyperkalemia May cause constipation

Furosemide 2-5mg/kg/od Hypertension oedema May be ineffective

Antihypertensives Depends on drug Hypertension

Erythropoietin 150U/kg/week (SC) Prevention / Rx of anaemia See text

93
References:
1. Pediatric Nephrology -4th Edition (1999) - Barratt, Avner, Harmon -Editors. Chapter 72, 1155-1182
Physiology and management
2. Pediatric Nephrology - 4th Edition (1999) - Barratt, Avner, Harmon- Editors. Chapter 74,1197-1230.
Endocrine and growth disturbances
3. Pediatric Nephrology - 4th Edition (1999) - Barratt, Avner, Harmon- Editors. Chapter 75, 1231 -1249.
Osteodystrophy
4. Pediatric Nephrology (1995) 9: 737 -741. Alphacalcidiol pulses normalize uremic hyperparathyroidism
prior to dialysis
5. Pediatric Nephrology (1999) 13: 143-147. Safety and efficacy of erythropoietin in children with
chronic renal failure
6. Pediatric Nephrology (1999) 13: 701-708. Phosphate binders for control of phosphate retention in
chronic renal failure
7. Role of nutrition in the care on children with renal insufficiency. Pediatr Clin N America (1982) 29:
973-990
8. Pediatric Nephrology- 2nd Edition (1987)- Holliday, Barratt, Vernier - Editors. Chapter 49, 773 -798
Progressive loss of renal function.

94
 CHAPTER 13

HYPERTENSION

Normal Blood pressure:

Systolic and diastolic pressures < 90th percentile for age and sex.

High normal blood pressure:

Average systolic and / or diastolic pressure 90-95th percentile for age and sex

Hypertension:
Average systolic and / or diastolic pressures > 95th percentile for age and sex on at least 3 separate
readings.

Significant hypertension:
Blood pressure 95 –99th percentile for age and sex

Severe hypertension:
Blood pressure > 99th percentile for age and sex.

Blood pressure normals in children:

• Premature neonate- See Figures 1-3 (J Perinatology 15: 470 –479)
• Age 1 – 12 months – See Second Task Force on blood pressure control in children – 1987 (Figure 4)
(diastolic BP is Korotkoff 4)
• Age 1-18 years – See 1996 Update on the 1987 Task Force Report (Figure 5) (diastolic BP is
Korotkoff 5)

Measurement:
The largest size cuff that can fit between the axilla and the elbow flexure, with the bladder completely
encircling the arm. Too small a cuff gives a falsely high reading.

According to the 1996 Task Force update, the diastolic blood pressure is taken as the 5th Korotkoff
sound – i.e. the disappearance of the sound and no longer the 4th (muffling). In patients in whom the
5th Korotkoff sound is not heard, the diastolic is not recorded. Diastolic readings from the 1996 Task
force are based on K5, not K4 and therefore tend to be lower. In the 1996 Task for BP is related to
height and sex.

95
Figure 1 Figure 2

Linear regression of mean systolic and diatolic Linear regression of mean systolic and
blood pressures by birth weight on day 1 of diatolic blood pressures by gestational age on
life, with 95% confidence limits (upper and day 1 of life, with 95% confidence limits
lower dashed lines) (upper and lower dashed lines)

Figure 3

Reference for Figures 1-3: Zubrow et

al. J Perinatology (1995) 15:470-9

Linear regression of mean systolic and

diatolic blood pressures by post-conceptional
age in weeks, with 95% confidence limits
(upper and lower dashed lines)
96
Figure 4 ♂ ♀

Age-specific percentiles for blood pressure in boys (a) and girls (b) from birth to 12 months of age.

From the Report of the Second Task Force on Blood Pressure control in children – 1987. Pediatrics
(1987) 79:5-6.

97
 ♂
Figure 5

From the Update on the 1987 Task Force Report on High Blood Pressure in children and
adolescents. Pediatrics (1996) 98:653.

98
Aetiology of persistent hypertension:
Secondary:
• Renal (31 –78%) – chronic renal failure, renovascular, renal parenchymal, renal tumours, obstructive
uropathy
• Cardiac (8-15%) coarctation of the aorta
• Endocrine (6-9%) –
• catecholamine excess – phaechromocytoma, neuroblastoma
• corticosteroid excess – Congenital adrenal hyperplasia (11 and 17 hydroxlase deficiency)
• thyrotoxicosis
• drugs – steroids oral contraceptives, ephedrine containing compounds (decongestants)
• Miscellaneous – raised intracranial pressure, burns, hypercalcemia, immobilization, autonomic –
Guillain-Barré, polio.

Primary (5-93%):
Essential hypertension profile: age > 12 years, female > male, family history of essential hypertension,
obesity, excessive salt intake Hypertension is mild and examination is normal – including no sign of end
organ hypertensive damage.

• The younger the age at diagnosis of hypertension and the greater the severity of the hypertension, the
more likely it is that the hypertension is secondary rather than primary.
• All patients with BP > 99th percentile, whether symptomatic or not, obese or lean, should be
investigated and treated,

History:
Often asymptomatic. Other: headaches, seizures, cardiac failure, stroke, Bell’s palsy, failure to thrive,
symptoms of the primary disease, drug ingestion. History of weight gain (Cushing’s), or weight loss
(thyrotoxicosis, phaeochromocytoma). Family history: early hypertension, renal disease. Past history of
umbilical artery catheterization

Examination:
Growth parameters, anaemia, rickets, obesity, signs of primary disease e.g. Cushing’s, ambiguous genitalia,
goitre. Skin – neurocutaneous syndromes, impetigo, vasculitis, facies – elfin (William’s syndrome), moon
face (Cushings), cardiac - failure, cardiomegaly (chronic hypertension), abdomen –masses: Wilm’s,
neuroblastoma, hydronephrosis, polycystic kidney disease, renal bruit, bladder (obstructive uropathy),
upper and lower limb blood pressures, femoral pulses – coarctation, neurological – Bell’s palsy,
encephalopathy, genitalia – ambiguous in CAH.

Investigations:
Preliminary screen: - (no clues as to diagnosis)

• Urinalysis (blood, protein, specific gravity) and mid stream urine culture – renal disease
• Chest X Ray, ECG +/- ECHO
• CBC, Hb electrophoresis
• Blood urea, creatinine and electrolytes (hypokalemia in hyperaldosteronism, hyperkalemia in renal
disease). Liddle’s syndrome (hyperkalaemic metabolic aklalosis and hypertension), Gordon syndrome
(hyperkalemic metabolic acidosis), serum calcium, phosphate, serum proteins, uric acid
• Calculate GFR – Schwartz formula (see Chapter 1
• +/- Fasting blood sugar (diabetes suspected), fasting lipoproteins
• Renal ultra sound (+ / - Doppler flow study of renal vessels) – (See Chapter 1)
• 24 hour urine VMA- VMA levels increased by bananas, asthma, and a methyl dopa
• Renal scan – DMSA , Glucoheptonate, DTPA – for scarring.
• Results suggesting renovascular disease:
• an asymmetric, non functioning kidney with a delayed time to maximum peak activity greater than
11 minutes, or less than 2 minutes to maximum activity after ACE inhibition;

99
 • asymmetric peak function;
• unilateral cortical retention of tracer after ACE inhibition,
• Decreased GFR in the ipsilateral kidney after ACE inhibition.
• RADIONUCLIDE SCANS (EVEN IF CAPTOPRIL ENHANCED) ARE NOT 100% RELIABLE
IN EXCLUDING RENAL ARTERY STENOSIS (RAS)

Captopril enhanced renography:

99m TcDTPA, or DMSA renal scan – a screening test for renovascular hypertension. Do baseline scan,
then Captopril 0.7/kg mg po (max 25 mg) given and scan repeated in 1 hour. A reduction in effective renal
plasma flow or GFR of > 40% may be helpful in identifying patients with “critical RAS”. (Paed Nephrol
1995 (9) 259 – 267). The scan is considered abnormal if a focal defect is seen or the differential function is
less than 45% (Eu J Nuc Med 20: 699 – 701 in Ped Neph 1995 (9): 387.

If the preliminary screen is normal and the profile for essential hypertension exists, the diagnosis is likely
to be essential hypertension, and further work-up may not be necessary. If the screen is normal, but the
essential hypertension profile is absent, investigate further.

Other investigations:
• Renal :MCUG, CT abdomen, renal biopsy, renal angiography or digital subtraction angiography.
Renin sampling from renal veins and vena cava ( Ratio of > 1.5 between plasma renin activity
(PRA) values in the main renal veils is a good predictor of surgical cure in renal artery stenosis).
• Phaechromocytoma: MIBG scan (123 I metaiodobenzylguanine scan – phaeochromcytoma tissue,
angiography, CT scan
• Aldosterone levels
o increased: urine mineralocorticoids, dexamethasone suppression test, adrenal scan
o reduced: other mineralocorticoids in urine and blood , cortisol response to ACTH and
dexamethasone
• Throtoxicosis – T4, TSH, T3 levels
• Cushings – cortisols
• Cardiac - ECHO, angiography

Treatment:
• Non pharmacological – weight reduction, exercise, diet – low sodium

• Pharmacological (see Table)

Aim to reduce blood pressure to below 95% for age
Discontinue ineffective drugs in a multidryg regime
Choose drugs with different sites of action
The stepped care approach is seldom used in children
Is combined with the non pharmacological treatment

Mild hypertension:
• Hydrallazine + /- diuretic(Furosemide if renal function abnormal, thiazides if function normal)

Moderate hypertension:
• Hydrallazine / B blocker / diuretic
• ACE inhibitor / diuretic
• Other second line drugs: Prazocin, nifedipine, α-methyl dopa (also used in severe hypertension)

100
Severe hypertension:
• Minoxidil + diuretic + second line drugs : Prazocin, nifedipine, α-methyl dopa
• Phaenoxybenzamine and phentolamine or prazocin – phaeochromocytoma

Hypertensive emergencies (see Table 3)

• Nifedipine, Hydrallazine, Minoxidil, Diazoxide, Sodium nitroprusside, Labetalol, Esmolol

101
Table 3
Antihypertensive drug therapy for hypertensive emergencies in children
Drug Dose
Hydrallazine 0.2 – 0.4 mg/kg IV titrated
or bolus or IM
or IV infusion 0.75 –5ug
/kg/min
Nifedipine 0.25 –0.5mg /g po
Minoxidil 0.1 –0.2 mg/kg po
Diazoxide 2.5 – 5 mg/kg (rapid IV
bolus) – maximum 150 mg
/dose
or 0.25 – 5.0ug/kg per min
by infusion
Sodium 0.5 – 1 ug/kg/ min IV
nitroprusside infusion initially – may be
increased stepwise to
8 ug /kg/min maximum
Labetalol 0.5–3 mg/kg/hr IV infusion
Nicardipine 0.5 -5ug /kg/ min IV
infusion
Clonidine 50 –300ug /kg/min IV
infusion
Enaprilat 0.005 – 0.01 mg/kg IV
q 8 – 24 hourly
1.25 mg IV q 6h
adolescents and adults
αmethyldopa 5 – 10 mg /kg (max
500mg) IV in 50 cc D5W
over 30 – 60 min – q 4 – 8
hrly
Phentolamine 0.1 – 0.2 mg /kg IV
Reserpine 0.02 – 0.07 mg/kg IM
q 2 – 3 h (max2.5mg/dose)
Onset of action Comments
10 –30 min May be repeated twice if no response
Give q 4h when bolus
Within20–30 min May be repeated twice if no response
Maximum initial dose 5 mg (q4h prn)
1-3 mins Can be repeated q 3 – 4 hourly
S/E hyperglycemia, salt and water
retention
Within seconds Light inactivated – ICU required –
cyanide and thiocyanate toxicity with
use > 72 hours or in renal failure– may
cause raised intracranial pressure
5-10 mins A and B blocker – contraindicated in
asthma / may worsen heart failure
Within min Calcium channel blocker – may increase
cyclosporin levels – can be diluted up to
50 mg in 100ml by peripheral vein
Within seconds Cardioselective B blocker – not
compatible with NaHCO3 – avoid if
asthma
Within 15 min ACE inhibitor – contraindicated if
severe renal artery stenosis present or
suspected
1 hour
A blocker - phaeochromocytoma
Rarely used nowadays – not
recommended for children
102
Table 4. Antihypertensive drugs for chronic hypertension in children

Drug Dose Dosing Comments

mg/kg/day interval

Labetalol 1-3 q 6 –12 h α /β blocker (contraindicated in asthma)

Phenoxybenzamine 1-4 Q 12 h α blocker - paheochromocytoma

Prazosin (Minipres) 0.05 – 0.5 Q 6-8 h α blocker

Atenolol 1-8 Q 12 – 24 h β blocker (contraindicated in asthma)

Propranolol β blocker (contraindicated in asthma)

1–8 Q 6 – 12 h Child
40 mg /dose Q q 12 h Adult / adolescent
(max 480mg/day)

Clonidine 0.05 – 0.6 mg Q6h α agonist

Nifedipine 0.25 – 3 Q4–6h Calcium channel blocker

Nifedipine XL 0.25 - 3 Q 12 – 24 h “ “ “
“sublingual” drug actually only works when
swallowed
Isradipine 0.05 – 0.15mg/kg/ dose Q6–8h
max 0.8mg/kg/day
max daily dose 20mg
Amlodipine 0.1– 0.3mg/kg/dose Q12 - 24 Calcium channel blocker
max 0.6 mg/kg/day Tablet can be suspended in water. Long acting –
max daily dose 20mg allow 5 – 7 days for dose adjustments – flushing
headache, lower extremity oedema, fatigue

Captopril 1.5 – 6 Q 8 – 12 h ACE inhibitor – “cough” may occur –

angioneurotic oedema potentially fatal allergic
reaction to ACE inhibitors – watch for
hyperkalemia

Enalapril ACE inhibitor

0.15 – 0.5 Q 12 – 24 h Children
2.5 – 40 (mg/day) Q 12 – 24 h Adolescents / adults

Rimipril ACE inhibitor

1.5 - 3mg/m2 Q 12 - 24 Children
2.5 – 10 mg /day Q 24 h Adolescents / adults

Hydrallazine 0.75 –7.5 Q 6h Vasodilator – lupus like syndrome

(maximum 200mg/day) Max dose 7.5mg/kg/dy or 200mg –
whichever is less

Minoxidil 0.1 - 2 Q 8 – 12 h Vasodilator – hypertrichosis – fluid retention –

pericardial effusion

αmethyldopa 10 - 65 Q 8 – 12 h Toxicity in renal failure – Peak effect in 7 days –

S/E depression, nasal congestion

103
Table 4 ctd
Antihypertensive drugs for chronic hypertension in children ctd

Drug: Dose Dosing interval Comments

mg/kg/day
Diuretics

Furosemide 1 - 12 Q 4 –12 h Loop diuretic

Ototoxicity in high doses
Bumetanide 0.02- 0.3 Q 4- 12 h

Hydrochlorothiazide 1-3 Q 12 – 24 h Thiazide – not for use in renal failure

Bendrofluazide 0.1 – 0.3 Q 12 – 24 h “ “ “ “ “ “ “

Metolazone 0.1 -3 Q 12 –24 h

Spironolactone 1-3 Q 6 – 12 h Aldosterone antagonist

Mineralocorticoid excess states – S/E
hyperkalemia – late onset

Triamterene 2-3 Q 6 – 12 h Mineralocorticoid excess states eg

Liddles syndrome – S/E hyperkalemia

Table 5
Oral antihypertensive agents for infants

Drug Dose Interval Comments

Captopril < 6 months: 0.01 – 0.05 mg/kg per Q8h Drug of choice for most neonatal
dose HTN – monitor serum creatinine
> 6 months as for child (maximum 6 and K+
mg/kg/day)

Clonidine 0.05 – 0.1 mg/dose Q 12 – 8 h S/E dry mouth and sedation –

rebound hypertension with
abrupt discontinuation

Hydralazine 0.25 – 1.0 mg/kg/dose Q8–6h Suspension stable up to 1 week;

(maximum dose 7.5 mg/kg/day) S/ E tachycardia & fluid
retention; lupus like syndrome
possible in slow acetylators

Isradipine 0.05 – 0.15 mg/kg/dose Q6h Ca channel blocker

maximum 0.8 mg/kg/day Suspension may be
compounded; useful for both
acute and chronic HTN
Amlodipine 0.1 – 0.3 mg/kg/dose Q 12 h Less likely to cause sudden
max 0.6mg/kg/day hypotension than isradipine can
be suspended

104
Table 5 ctd

Oral agents for hypertension in infants - ctd.

Drug Dose Interval Comments

Labetalol 1 mg/kg/dose Q 12 – 8 h Monitor HR / avoid in infants with

max 10 mg/kg/day BPD and / or bronchospasm

Sprionolactone 0.5 – 1.5 mg/kg/dose Q 12 h Monitor electrolytes

Minoxidil 0.1 – 0.2 mg/kg/dose Q 12 – 8 h Used for refractory HTN

Propranolol 0.5 – 1.0mg/kg/dose Q8h Avoid in infants with BPD and

max 8 – 10 mg/kg/day if HR bronchospasm
normal

References:

Antihypertensives for infants and fetal BP values: - Pediatr Neph (2000) 14: 332 – 341
Antihypertensive agents:
calcium channel blockers – Pediatr Neph (2000) 15: 302 –316
amlodipine – Pediatr Neph (2000) 14: 1083 – 1087
nicardipine – Pediatr Neph (1998) 12 40 –42
loop diuretics – Pediatr Neph (1998) 12: 603 – 616

ACE inhibitors
Enalaprilat – Pediatr Neph (2001) 16: 85 – 86
Rimipril – Pediatr Nephr (2000) 15: 113 – 118

Treatment of hypertensive emergencies in children

Pediatr Neph (2000) 14: 422 – 427
Pediatrics (1996) 98: pg 655 – Task force update

Treatment of hypertension in children

Pediatrics (1996) 98: pg 656
Pediatr Nephrol (1987) 1: 50 – 58
Pediatric Nephrology 4thEdition – pages 1038, 1039, 1046

Hypertension in children – investigation and treatment

Pediatr Nephrol (1987) 1: 59 – 68
Pediatric Nephrology – 4th Edition – Barratt, Avner, Harmon eds – Lippincott Williams & Wilkins Pub. –
1999 edition / Chapters 60 – 63 / pages 959 – 1049

Captopril studies for renovascular hypertension

Pediatr Nephrol (1991) 5: 42 – 44
Ped Nephrol (1995) 9: 259 – 269
Pediatr Nephrol (1997) 11: 366 – 372

105
 CHAPTER 14

DISORDERS OF ACID / BASE BALANCE

Acid / base homeostasis is maintained by a combination of metabolic and respiratory factors. Although the
first line of defense is the buffer system and respiratory factors, final correction rests with the kidney. For
the purposes of investigation, measurement of the pCO2 reflects the respiratory component and HCO3- the
metabolic component.

Acid base profile is best assessed by:

• Measurement of pH, pCO2, HCO3 (arterial or venous blood gases)
• Measurement of anion gap in plasma and urine -(measure serum Na, Cl and HCO3,and urine Na,
K, Cl )
• Consulting an acid / base nomogram (See Figure 1)

Normal values

PH, pCO2, HCO3 – (see Chapter 1)

Anion gap – (blood) = [Na ] - [Cl + HCO3] = 8 – 16 mEq/l

Useful in evaluating metabolic acidosis (see Figure 2)

Anion gap – (urine) = [UNa + UK] - [U Cl ]

Useful in distinguishing proximal from distal renal tubular acidosis (RTA)

Measures, indirectly, the urine concentration of ammonium in a patient with hyperchloraemic metabolic
acidosis
Negative urine anion gap [Cl >> Na +K] - GI or Renal loss of HCO3
Positive urine anion gap [Cl < Na + K] - Distal acidification defect

Common acid / base abnormalities

Type pH pCO2 HCO3

Respiratory acidosis (acute) N or slightly

Respiratory acidosis (chronic) (slightly)

Respiratory alkalosis (acute) N or slightly

Respiratory alkalosis (chronic) N or

Metabolic acidosis

Metabolic alkalosis N or

106
 Figure 1

Acid Base
Nomogram

An in vivo acid-base nomogram for clinical use. Usually acid-base values falling within a shaded band
indicate a single disturbance. Acid –base values falling outside shaded bands indicate there are at least
two acid – base disturbances. (From Arbus GS. An in vivo acid-base nomogram for clinical use. Can
Med Assoc J 1973; 109: 291)

Guidelines:

Chronic respiratory acidosis:

For every 3mmHg increase in pCO2 - HCO3 increases by about 1Eq/l (3:1 ratio)

Metabolic acidosis:
For every 1mEq/l decrease in bicarbonate - pCO2 decreases by 1mmHg (1:1 ration)

In simple disturbances of acid –base balance - CO2 and HCO3 change in the same direction

In mixed disturbances of acid – base balance - CO2 and HCO3 change in opposite directions

Respiratory acidosis – impaired ventilation – Rx ventilation – not bicarbonate

Respiratory alkalosis – hyperventilation – Rx correct primary cause

107
Metabolic alkalosis – Rx primary cause
Causes include
• Hypochloremia
• Bicarbonate overdose
• Volume depletion (eg diuretic overdose)
• Hypokalemia (eg Bartter syndrome)
• Phosphate excess

Metabolic acidosis - serum bicarbonate < 20mEq/l

Figure 2: Evaluation of Metabolic Acidosis

Anion Gap

Normal Increased

Organic acids Exogenous acid load

Lactate –shock, hypoxia Salicylates
Ketoacids – diabetes Paraldehyde
Organic acidopathies Methanol
eg Propionic acidemia Ethylene glycol

Uraemia

Check urine pH

< 5.5 > 5.5

GI bicarbonate Proximal RTA

Losses in severe acidosis RTA

Ingestion of acid with Cl as anion severe acidosis or NH4Cl (Acid) loading test
e.g NH4Cl, arginine or lysine HCL

UpH UpH
<5.5 >5.5

Proximal RTA Distal RTA

108
Figure 3: Evaluation of hyperchloraemic metabolic acidosis and negative urine anion gap

Negative urine anion gap

[Cl > Na + K]

GI HCO3 loss Proximal RTA HCl intake

History History

Urine Na Acid NH4 load

UpH < 5.5

Sodium bicarbonate load

FE HCO3 > 10 – 15%

U-B pCO2 > 20 mmHg

Proximal RTA

Look for other tubular defects

FE HCO3 – fractional excretion of bicarbonate; U-B PCO2, urine to blood pCO2 gradient

From Renal tubular acidosis - Rodriguez-Soriano and Vallo. Pediatr Nephrol (1990) 4: 273

109
 Figure 4: Evaluation of hyperchloraemic metabolic acidosis and a positive anion gap

Positive urine anion gap

[Cl < Na + K]

Distal renal defect

Plasma K

Normal – Decreased Increased

Acid load

UpH >5.5 >5.5 <5.5

Sodium bicarbonate load

FE HCO3 <5% < 5% >5 to 10%

U-B pCO2 < 20mmHg < 20mmHg > or < 20mmHg

(depends on GFR)

Distal RTA Hyperkalaemic RTA

Secretory defect Voltage defect ?hypoaldosteronism-TTKG

Look for nephrocalcinosis, Look for Na ? renal disease

Hypercalciuria and hypocitraturia transport defect

From Renal tubular acidosis Rodriguez-Soriano andVallo. Pediatr Nephrol (1990) 4:273

Renal tubular acidosis:

• Definition: metabolic acidosis secondary to transport defects in the reabsorption of bicarbonate, the
excretion of hydrogen ions or both
• relatively normal GFR
• hyperchloraemic metabolic acidosis
• normal plasma anion gap
• not to be confused with uraemic acidosis – advanced renal failure/ normochloraemic metabolic
acidosis and increased plasma anion gap

110
Classification of RTA

Proximal (Type 2)
• caused by impairment of HCO3 reabsorption in proximal tubule
• decreased renal HCO3 threshold
• able to acidify urine to pH < 5.5 in severe metabolic acidosis (when plasma HCO3 sufficiently low)
• requires large amount of bicarbonate for correction as fractional excretion of bicarbonate is high
(10 –15%)
• aetiology: isolated or accompanied by other tubular defects (Fanconi syndrome)
• characterized by growth retardation
• rickets and osteomalacia never seen except with hypophosphataemia in Fanconi syndrome
• nephrolithiasis and urolithiasis never occur even in presence of hypercalciuria
• hypokalaemia restricted to Fanconi’s syndrome
• Fanconi syndrome – multiple tubular defects: generalized aminoaciduria, renal glycosuria,
phosphaturia, bicarbonaturia (proximal RTA), hyperkaliuria, sodium wasting, uricosuria, proteinuria,
and hyposthenuria, growth failure and vitamin D resistant rickets

Distal (Type 1)
• caused by impairment of distal acidification – usually failure of H+ pump
• characterized by inability to maximally reduce urine pH (<5.5) in systemic acidaemia
• impaired NH4 excretion
• HCO3 reabsorption is quantitatively normal, but some bicarbonaturia may exist (<5% of filtered load)
– less bicarbonate is required for correction
• K usually normal or decreased
• with “voltage dependent” defect, impaired K secretion results in hyperkalaemia - Hyperkalaemic
distal RTA (Type 4 RTA)
• characterized by growth retardation, polyuria, hypercalciuria, nephrocalcinosis, lithiasis and K
depletion
• usually primary (genetic defect) in children and acquired in adults often with autoimmune disease

Combined proximal and distal RTA (Type 3)

• features of both proximal and distal RTA
• marked reduction in tubular reabsorption of filtered HCO3 but ability to acidify the urine maximally
despite severe systemic acidaemia
• usually a transient phenomenon in infants and young children with primary distal RTA

Hyperkalaemic RTA (Type 4)

• acidification defect mainly caused by impaired renal ammoniagenesis
• characterized by normal ability to acidify urine after an acid load, but subnormal acid excretion due to
very low rate of NH4 excretion.
• Most frequently seen in children with hypo- or pseudohypo- aldosteronism
• May be isolated or found with chronic renal parenchymal damage
• Nephrocalcinosis and lithiasis are absent
• Bone lesions are seen with uraemic patient
• Hyperkalemia always present

111
 Aetiology of Proximal and Distal RTA

Proximal Distal

With Fanconi syndrome Idiopathic

• Inborn errors of metabolism Auto – immune (SLE)

(eg galactosaemia, cystinosis)

• Chronic hypocalcaemia with secondary Inherited – sickle cell disease, Marfan synd
hyperparathyroidism
eg vitamin D deficiency and bowel disease

• Drugs eg lead Nephrocalcinosis 20 to hyper-

parathyrodism, hyperthyroidism, Wilson’s
disease

• Renal – nephrotic syndrome, medullary Drugs – Lithium, amphotericin B

cystic disease

Isolated defect of proximal HCO3 reabsorption

• Idiopathic
• Acetazolamide

CLINICAL EVALUATION OF A PATIENT WITH SUSPECTED ACID-BASE DISTURBANCE

History:
Polyuria, polydypsia, failure to thrive, recurrent fevers, renal stones, sickle cell disease, SLE, drug
ingestion

Examination:
Growth parameters, BP, hydration, stigmata of syndromes, rickets

Investigations:
Blood urea, creatinine and electrolytes (including bicarbonate), serum calcium, phosphate, albumin,
alkaline phosphatase, venous blood gases – pH, pCO2, and bicarbonate (See Chapter 1)

Urine:
• PH (Chemical Pathology by special arrangement) – dipstix UpH is not accurate
• Urinalysis – protein, sugar, blood, and microscopy for cells and casts
• Clinitest for reducing sugars
• Amino acid screen (Chemical Pathology)
• Spot urine calcium, sodium, potassium, phosphate, protein, creatinine +/- 24 hour urine phosphate -
calculate tubular reabsorption of phosphate, hyperphosphaturia, check for hypercalciuria, and
excessive sodium and potassium loss in face of hypo- natraemia / hypokalaemia (See Chapter 1)
• Urine specific gravity (fasting – if safe to do so) – assess concentrating ability

If Type 4 RTA suspected: add urine and plasma osmolality to calculate TTKG (See Chapter 1)

112
Management of metabolic acidosis
• Treat underlying cause
• Correct acidosis if HCO3 < 12mEq/l or pH < 7.2 by formula below:

HCO3 required = [HCO3 desired - HCO3 initial] x 0.6 x body weight (kg)
HCO3 desired = 12 mEq/l

• Give half over 10 – 15 minutes and the remainder as an infusion over 2 – 3 hours.
• Reassess acid-base status after treatment
• Do not infuse with calcium containing preparations (precipitation)

Treatment of RTA
• Treat underlying cause if identified
• Give bicarbonate supplements sufficient to maintain serum bicarbonate at 20 – 25 mEq/l to ensure
optimal growth. Sodium bicarbonate (baking soda) is used, though citrate preparations are sometimes
available
• Proximal RTA will require more bicarbonate supplementation than distal RTA (10 –25 mEq/kg/day)
as opposed to distal RTA (5 – 15mEq/kg/day). K supplements may be needed in Types 1 and 2 RTA
as K loss in the urine occurs
• Follow growth – height and weight
• Regular measurement of bicarbonate levels, renal function and urine calcium /creatinine ratios
• +/- abdominal ultrasound for renal length and calcification, if nephrocalcinosis present at diagnosis
• +/- plain abdominal X (PA) for following nephrocalcinosis
• Type 4 RTA – + / - mineralocortoids (Fludrocortisone), +/- K binders (Resonium A)

FORMAL PROTOCOL FOR LABORATORY EVALUATION OF SUSPECTED RTA

1. Make prior arrangement with Chem Path for measurement of urine pH and chloride, and ICU for blood
gases

2. No food after midnight. Discontinue alkali therapy for at least 6 – 12 hours before test (or ideally
perform the test when spontaneously acidotic).

3. At 8 am

• record height, weight, body surface area (m2) (see Chapter 1), BP, pulse and hydration
• blood: electrolytes, urea, creatinine, bicarbonate, venous blood gas – heparinized syringe for pH,
pCO2, and calculated bicarbonate (ICU) +/- plasma osmolality (Type 4 RTA)
• urine: spot Na, K, Cl ,Ca, Creatinine, phosphate, amino acid screen, pH (Chem Path)
specific gravity (refractometer or hygrometer), dipstix for protein, blood and sugar
microscopy (centrifuged) for cells, casts)

4. Calculate urine and blood anion gap (see above)

5. Follow Figures 2 – 4 – using urine anion gap to assist in diagnosis

6. Generalizations to aid evaluation:

• If urine pH < 5.5 and plasma bicarbonate < 18 mEq/l - likely – proximal RTA
• If urine pH > 5.5 and plasma bicarbonate < 18 mEq/l – likely – distal RTA
• If urine pH > 5.5 and plasma bicarbonate > 18mEq/l < 20mEq/l ? distal RTA do NH4 Cl acid
loading test

113
 Ammonium chloride (Acid) loading test

0800 IV D5 in normal saline at 50ml/m2/hr with oral fluids ad lib and normal diet

0900 NH4 Cl 100mg / kg po in gelatin capsules or lemonade (order from pharmacy)

1000 urine pH

1100 urine pH

1200 urine pH, serum electrolytes, urea, creatinine and bicarbonate, and venous gases for bicarbonate
pCO2 and pH

1300 urine pH

1400 urine pH, blood tests for 1200

• Peak effect is 4 hours after dose.

• Abort test when serum bicarbonate is < 15 mmol/l
• Interpret results as per figure 3 and “Generalizations” above

References:
1. Renal and electrolyte disorders – 2nd edition (1980). Schrier ed. Little, Brown and Co Pub: 115 – 158,
159 – 182
2. Renal tubular acidosis in children. McSherry. Kidney Int (1981) 20: 799 – 809
3. Pediatr Nephrol (2000) Rodriguez- Soriano. 14: 1121 – 1136. New insights into the pathogenesis of
renal tubular acidosis – from functional to molecular studies
4. Pediatr Nephrol (1990) 4: 268 – 275 Rodriguez-Soriano and Vallo. Renal tubular acidosis
5. Residents Handbook – Hospital for Sick Children – 7th edition. Abelson and Smith (1987), pages 142 –
145, 394 - 395

114