Renal Function Test

Renal function tests
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Dr Jayadeep B P
I MD Repertory
jayadeepbp@gmail.com, 9447545802
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Functions of kidney
• Excretion of Metabolic Waste Products,
Foreign Chemicals, Drugs, and Hormone
Metabolites
• Regulation of water - electrolyte balances,
body fluid osmolality
• Regulation of arterial pressure
• Regulation of acid-base balance
• Regulation of Erythrocyte Production
• Regulation
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of 1,25–Dihydroxyvitamin
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D3
OBJECTIVES
• To detect possible renal
damage and assessment of its
severity
• To diagnose renal disease
• To observe the progress of
renal disease
Gives information
• Renal blood flow
• Glomerular filtration
• Renal tubular function
• Urinery out flow unhindered by
any obstruction
4 groups
• Urine analysis
• Concentration & dilution tests
• Blood chemistry
• Renal clearance tests
Urine analysis
• physical examination
• chemical examination
• Bacteriological and
• Microscopic examination
physical examination
• 24 hour urinery out put [volume]
• Appearance, Colour, Turbidity
• pH
• Specific gravity
• osmolality
Volume
• Volume is a measure of
glomerular filtration and tubular
reabsorption
• 1.5 L/24 hr - typical in health
• Children: 1.5 ml/Kg of b.w./1

hour!
• Dependent upon subject’s activity,
hydration status, diet and body size
• Temperate climates: output of 800-
2500 ml urine per day is usual
• Sudden changes in volume of urine
can indicate problems with ability to
concentrate urine
Oliguria
– Urine volume less than 400 ml/24 hours or < 1 ml/kg
- in hypotension or hypovolaemia
- intrinsic renal pathology
Anuria < 100 mL
• Total anuria is usually due to obstruction in the urinary tract.

Polyuria – urine output of > 2 litres/24 hours
• disturbance in the tubular concentrating

capacity or ADH failure [ diabetes insipidus]
• increased osmotic load (diabetes mellitus)
• excessive water intake (physiological response)
• drug-induced (outdated tetracycline, lithium)
• deficiency of vasopressin
Colour -appearance
• Normally
Amber light
coloured
• Very clear
urine with
high
discolouration
Deep yellow - Concentrated urine, Jaundice
• Red urine - Haematuria, Haemoglobinuria
Myoglobinuria, Porphyria, Beet root ingestion
Drugs - rifampicin, pyridium
• Cloudy -Infection
• Milky – Chyluria, Pyuria, Phosphaturia
• Dark on standing –Porphyria, Alkaptonuria

Turbidity
• Infection
• Nephrotic syndrome
• proteinuria

Osmolality
• Measures urine concentrating ability
• normal - 400-900 mOsm/Kg H20
• Can reach Max - 1200 mOsm/Kg H20
• useful for determining whether ionic imbalances
exist in subject
• Depends on # of particles, not size or charge
• Largely due to ADH
• prior to collection, fluid intake restricted
• first void submitted for evaluation
Urinary pH
• Normally acidic
• Normal range - 4.5-8[5-9]
• diagnostic significance- when it is
studied serially in response to
acid load in suspected renal
tubular acidosis
Specific gravity
• A measure of density of urine measured with
density of water
• with a refractometer or urinometer
• gives rough estimate of osmolarity
• Normal -1.003 – 1.030 ; Average - 1.018
• The higher the number = the more
concentrated urine
• A fixed specific gravity of 1.010 is
• increased
Lack
decreased
Dilute
ofurine
fluids

Chemical tests
presence of
To assess the
•
•
permeability
of glomerular
membrane

Using dipstick tests
-paper strips impregnated with appropriate reagents & indicator dyes
- Modern dipsticks with multiplied zones -For Protein, hemoglobin,
glucose,
18.09.10 urobilinogen, nitrite, leukocytes, specific gravity,
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Protein
• A 24-hour urine collection and
measurement of protein is the
most accurate
• Normally small amount of protein
is excreted in the urine which
may not exceed 150 mg/24 hours
Dipstix test
• a paper strip impregnated with bromophenol
blue dye which changes to blue in the
presence of protein at a suitable pH (pH 3)
• As the strip has a yellow background the
colour change is observed as green
• The intensity of green is proportional to
concentration of protein in urine
• Disadvantages - colour change is pH-
Acid precipitation test
• A more sensitive but less specific test
• Eight drops of sulphosalicylic acid are added to
2 ml of urine
• A precipitate forms in the presence of protein
• Light chains and low-molecular-weight
proteins are detected by this technique
• False positive results occur with penicillin, PAS,
etc
magnitude of proteinuria
• Mild - chronic interstitial disease, febrile
illness and congestive cardiac failure
• Small amount - severe urinary tract infection
or obvious haematuria
• Large amount (3 g/day or more) - glomerular
disease.

urine protein/urine creatinine ratio
• When 24 hours’ collection of urine is difficult
or impractical as in children or patients with
urinary fistulae, urine protein/urine creatinine
ratio can be calculated in spot urine sample
• Due to diurnal variation the best sample is
obtained at mid morning
• < 0.3 - normal
• 0.3 - 3.0 - abnormal
Microalbuminuria
• Conventional methods cannot detect urinary
albumin excretion of 20 to 200 microg/min,
referred to as microalbuminuria
• useful test for detecting incipient diabetic
nephropathy
• The urine sample is collected under standard
conditions after rest of 2 hours, overnight (8
hours) or early morning.
• Bence-Jones proteins are light chains excreted
by patients suffering from monoclonal
gammopathies.
• It is not detected by dipstix and is best
identified by immunoelectrophoresis of urine

Glucose
• Benedict’s test
• Dipstix are specific
• Normally –ve
+ve urine glucose

– Increased blood glucose
– Low renal threshold
– Other tubular diseases
False +ve
Blood
• very sensitive
• 2 or more cells can produce result
• Sometimes TOO sensitive, giving false
positives
• Can’t distinguish between blood and free
Hb, so usually double-check with
microscope.

• Ketone bodies -ve
• Bilirubin -ve
• Nitrites –ve & positive when UTI with gram +
ve bacteria

Bacteriological examination
• By proper & aseptic

collections of mid
stream specimen of
urine
• The presence of any
Urine Microscopy
• The genitalia
should be
cleaned with
Sterile pyuria • Tuberculosis should
• acute febrile be suspected in
episode, recurrent sterile
pyuria;
• glucocorticoid
therapy,
• it can also be due to
fungi, atypical
• cyclophosphamide mycobacteria, H.
administration, influenzae,
• pregnancy, anaerobic bacterias
etc
• renal transplant
rejection,
- in renal
18.09.10 diseases,www.similima.com
lower UT diseases,can be
3636in exercise
RBCs-in lower UT bleeding

glomerular bleeding (teardrop forms)

Click to edit Master subtitle style
Epithelial cells 0-2 HPF

-Increased in bladder inflammation,tubular injury etc
Casts
• Cylindrical bodies formed by coagulation of

Tomm-Horsfall glycoprotein within the tubules
• hallmark of renal parenchymal disease
• The material contained within the tubular
lumen at the time of cast formation gets
entrapped within the cast
• often seen normally after exercise
• Granular cell casts-coarse
• Non specific; Can seenwww.similima.com
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• Coarse
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granular casts In aute tubular necrosis
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• Seen in acute glomerulonephritis
Hyaline casts
- Nonspecific; Present in normal urine
- Concentrated urine, febrile disease, after strenuous exercise,
Epithelial
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cell casts-In renal4848
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• Waxy • Advanced renal failure
• Fatty • Nephrotic syndrome
Fabry's disease
Other nephritidis
• Proliferative GMN (SLE,PAN)
• Mixed
• Bacterial
• Bacterial pyelonephritis

• Pseudocasts are
composed of clumped
urates, leucocytes and
bacteria
Crystals
• Triple phosphate and calcium oxalate crystals
may be found even in normal urine and are
not significant
• Other crystals identifiable in abnormal urine
are of cystine, sulphonamides,urates etc.

Triple phosphate crystals
• - 18.09.10
‘coffin lid’ appearance
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Calcium oxalate crystals
- occur at any ph
- resembles an ‘envelope’
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Urate crystals

Concentration & dilution tests
• Aim
To evaluate functional capacity of renal
tubules
• Ability of nephron to do so –dependent upon
Functional activity of tubular cells in renal
medulla & Presence of ADH

• Failure to achieve adequate urinery
concentration due to Defects in renal medulla
[NDI] or Lack of ADH [CDI ]
• Traditionally Concentration is determined by
Specific gravity of urine gives rough estimate
of osmolarity

Water deprivation or concentration
test
• To diagnose tubular disease in
early stage
PROCEDURE
• Artificial fluid deprivation for > 14
hrs
• If the nephron is normal ,water is selectively
reabsorbed & excretion of urine of high solute
concentration [SG-1.025 or more] with an
osmolality exceeds 850 mOsm/kg
• If tubular cells are non functional solute
concentration remains constant regardless of
stress of water deprivation
• The test should not be performed on a
dehydrated patient
Dilution test/water excess tests
• After an overnight fast the patient empties his
bladder completely and is given 1000 ml of
water to drink
• Urine specimens are collected for the next 4
hours, the patient emptying bladder
completely on each occasion
• Unless there is renal functional impairment,
the patient will excrete at least 700 ml of urine
in the 4 hours, and at least one specimen will
• Kidneys which are severely damaged cannot
excrete a urine of lower specific gravity than
1.010 or a volume above 400 ml in this time.
There is a delayed diuresis
• Abnormal results are also found if there is
delayed water absorption or adrenal cortical
hypofunction
• If renal tubules are diseased the concentration
of solutes in the urine remain constant
Other tests
VASOPRESSIN TEST
• depends only on renal tubular function
• At 8 pm-five units of vasopressin tannate is
injected subcutaneously
• All urine samples are collected separately until
9 a.m. the next morning
• Satisfactory concentration is shown by at least
one sample having a specific gravity above
DYE EXCRETION TESTS
• Using Phenolsulphonphthalein (phenol red)
• Indigo-carmine
• Its excretion essentially tests for renal plasma
flow and is therefore impaired early in
conditions such as heart failure.

Blood chemistry
• Impairment of renal function leads to
elevation of end products of protein
metabolism
• thus increased accumulation of urea,BUN, &
creatinine in blood & azotemia results

Urea
• end-product of protein metabolism chiefly
excreted through the kidney
• It is filtered by the glomeruli and variably
reabsorbed in the tubules
• The normal plasma concentration is 20-40
mg/dl
• Blood urea concentration is about 14% less
than plasma concentration
• Raised
High-protein
Low
Low-protein diet
diet

BUN
• Normal BUN range is 8-25 mg/dL
• It is not possible to detect renal damage by a
raised BUN until renal function has fallen by
about 50 percent as measured by the
creatinine clearance test
• estimation is most useful for the assessment
of the severity and progress of renal failure in
• Acute tubular necrosis, Acute
glomerulonephritis, Chronic renal disease,
Post-renal obstruction
Creatinine
• The breakdown • increased
product of creatine increased
phosphate released
from skeletal muscle
• Impaired renal
at a steady rate. function
• It is filtered by the
• Very high protein
glomerulus. diet
• more sensitive and
• Anabolic steroid
specific test than users
• Serum creatinine is the most widely used
marker for GFR, and the GFR is related directly
to the urine creatinine excretion and inversely
to the serum creatinine
• If GFR suddenly decreases by 50%, the kidneys
will transiently filter and excrete only half as
much creatinine, causing accumulation of
creatinine in the body fluids and raising
plasma concentration
Uric Acid
• Increased
• Metabolite of purine • Renal failure
metabolism • Gout
• Liver and
• Filtered by the sweetbread
glomeruli and both gourmets
reabsorbed and • Lead poisoning
secreted by the renal
tubules
• Thiazide diuretics
• High dose aspirin
BUN/creatinine ratio
• > 15 is abnormal and indicates pre or post
renal azotaemia
• elevated in all conditions associated with urea
overproduction
• A low ratio is found in pregnancy,
overhydration, severe liver disease, and
malnutrition.
• The ratio is normal in renal azotaemia
Renal clearance tests
• To assess GFR & renal blood flow
• “renal clearance of a substance is the
volume of plasma that is completely
cleared of the substance by the
kidneys per unit time”

clearance principle
• If the plasma passing through the kidneys
contains 1 milligram of a substance in each
milliliter and if 1 milligram of this substance is
also excreted into the urine each minute, then
1 ml/min of the plasma is “cleared” of the
substance.
• Thus, clearance refers to the volume of plasma
that would be necessary to supply the amount
of substance excreted in the urine per unit
Re arranged as
• Cs = Us × V
Ps
• Cs = clearance rate of a substance ‘s’
• Ps = plasma concentration of the substance
• Us = urine concentration of that substance
• V = urine flow rate[volume in ml/min]

Estimation of GFR
• If a substance is freely filtered and is not
reabsorbed or secreted by the renal tubules,
then the rate at which that substance is
excreted in the urine is equal to the filtration
rate of the substance by the kidneys
• GFR = Us × V /Ps =Cs
• Thus here equal to clearance of that substance
• Normal GFR -120 + 25ml/min/1.73m2
Inulin or mannitol clearrance test
Innulin
• Ideal substance
• a polysaccharide molecule
• molecular weight of about 5200
• not produced in the body, is found in the roots
of certain plants
• Its filtered from the glomerulus & is excreted
unchanged in urine
Creatinine clearance test
• does not require intravenous infusion

• method is much more widely used than
inulin clearance for estimating GFR clinically
• creatinine clearance is not a perfect marker
of GFR because a small amount of it is
secreted by the tubules so that the amount
of creatinine excreted slightly exceeds the
METHOD
• A careful and accurate 24 hour
collection of urine is made at some
time during the day (but not within
1-3 hours after a large meal)
• a blood sample is taken for plasma
creatinine analysis

• Creatinine clearance =
Ucr × volume [ml] x 1.73/A
Pcr × time [min]
• Ucr = Urine creatinine concentration
• Pcr = Plasma creatinine concentration
• V = Urine flow in ml/min
• A = Body surface area in m2 and
According to
Cock Croft and Gaut formula
• When Errors in 24 hours urine collection
creatininine clearance is calculated from
plasma creatininine concentration which
incorporates age, sex, and weight to estimate
Ccr from plasma creatinine levels without any
urinary measurements

• Creatinine clearance :
140 - age (years) X wt (kg)
Serum creatinine (mg/dl) x 72 for men
• For women, the estimated GFR is multiplied
by 0.85 because muscle mass is less
• This formula overestimates GFR in patients
who are obese or edematous, and is most
accurate when normalized for body surface
• normally 90-130 ml/min in an adult of normal
size
• approx- 100 mL/min/1.73 m2 in healthy young
women
• 120 mL/min/1.73 m2 in healthy young men
• The Ccr declines by an average of 0.8 mL/min/
yr after age 40 years as part of the aging
process
Urea clearance test
• No need of IV infusion
• Less sensitivity test
• Cz plasma concentration of urea is affected by
number of factors
• Like dietary protein,fluid intake, inflammation,
trauma, surgery, corticosteroids
• Partly reabsorbed from tubules

Others
• Other substances for GFR
estimation- radioactive
iothalamate and EDTA and DTPA
(=both derivates of acetic acid) &
cystatin C

Para amino hippuric acid [PAH]
clearance tests
• To measure renal blood flow
• When IV infusion of PAH, both
filtration at glomerulus &
secretion by tubules

• if a substance is completely cleared from the
plasma, the clearance rate of that substance is
equal to the total renal plasma flow
• Because the GFR is only about 20 per cent of
the total plasma flow, a substance that is
completely cleared from the plasma must be
excreted by tubular secretion as well as
glomerular filtration

• The percentage of PAH removed from the
blood is known as the extraction ratio of PAH
and averages about 90 per cent in normal
kidneys
• Therefore, the clearance of PAH can be used
as an approximation of renal plasma flow
• In diseased kidneys, this extraction ratio may
be reduced because of inability of damaged
tubules to secrete PAH into the tubular fluid
• Total renal plasma flow =
Clearance of
PAH/Extraction ratio of PAH
• Thus Total renal plasma
flow is 650 ml/min
Renal blood flow
• If the hematocrit is 0.45 and
total renal plasma flow is 650
ml/min
• RBF = 650/(1 - 0.45) = 1182
ml/min

Renal failure indices
• Two important diagnostic indices are the renal

failure index and fractional excretion of
filtered sodium.
• Renal failure index (RFI)
= Urine sodium (mEq/L) x Plasma
creatinine (mg/dl]
Urine creatinine (mg/dl)
summary
• Examination of the urine is the most
important initial test for suspected renal
damage, particularly glomerular diseases.
• Search must be made for protein, erythrocytes
and casts.
• The urine concentration test (or vasopressin
test) is sensitive. It is possibly the most useful
single test for confirming the presence of renal
tubular impairment.
To see the structural integrity
• Plain X-ray KUB

• IVP
• Cystoscopy
• Excretion urography
• Ultrasonography
• Computed tomography (CT)
• Magnetic resonance imaging (MRI)
• Antegrade pyelography
• Retrograde pyelography

{83F0094B-1A13-460B-AECE-0B0E67848A54}
Thank you

• Sodium (varies with intake) 100–260 mmol/d
100–260 meq/d
• Potassium (varies with intake) 25–100 mmol/d
25–100 meq/d
• Calcium (10 meq/d or 200 mg/d dietary
calcium) <7.5 mmol/d <300 mg/d

• It is possible to test the ability of the kidney to
• conserve sodium by giving a diet containing 20
• m mol sodium/day. Normally the urinary
sodium
• excretion should fall to the amount present in
• the diet within a week. This test should always
• be monitored with great care by daily
• Measurement of urinary potassium output
may
• provide valuable data in patients suspected of
• having abnormal losses. If dietary potassium is
• reduced to 20 m mol/day, urinary output
should
• fall to this value within one week (occasionally
• this takes two weeks) in healthy individuals.
• RENAL FUNCTION WITH INCREASING AGE
• There is a gradual decrease in all aspects of
renal function after 35 years of age. This
• appears to be due to involution, but may be
• aggravated by renal vascular degeneration.
The
• most clinically significant change is the gradual
• reduction in GFR which, when accompanied

Renal Function Test

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Renal function tests

• 1.5 L/24 hr - typical in health

• Children: 1.5 ml/Kg of b.w./1

Anuria < 100 mL

• Total anuria is usually due to obstruction in the urinary tract.

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• disturbance in the tubular concentrating

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+ve urine glucose

– Low renal threshold

– Other tubular diseases

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• By proper & aseptic

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Epithelial cells 0-2 HPF

• Cylindrical bodies formed by coagulation of

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• does not require intravenous infusion

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• Two important diagnostic indices are the renal

• Plain X-ray KUB

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