Abnormal

Urinalysis in
Children:
Proteinuria and
Hematuria
dr. Kristia Hermawan, MSc, Sp.A

Division of Pediatric Nephrology

Department of Child Health
Faculty of Medicine, Universitas Gadjah Mada
Sardjito Hospital Yogyakarta
2013
 Abnormal Urinalysis in Children:
Proteinuria and Hematuria

PROTEINURIA
 Introduction
Protein in urin (under normal circumstance)
60% derived from plasma protein (albumin n 30 others)
40% urinary tract secretion (mucoprotein, secretory IgA,
tubular epithelial cell)

Normal urinary protein loss:

10-15 mg albumin / 24 hours
25 mg Tamm-Horsfall mucoprotein / 24 hours

Significant proteinuria associated with progressive

renal disease
 Definition
Normal Abnormal Nephrotic
Urine test protein protein range
excretion excretion proteinuria
Dipstick Negative 1+ 2+ for 3
or trace consecutive
days
Sulfosalicylic acid Negative 1+ 2+ for 3
test consecutive
days
24 hour protein
excretion 0.15 > 0.15 3
g/day/1,73m2: 4 >4 40
mg/m2/hour:
Protein cretainin
ratio
(g/mmol) 0.02 > 0.02 0.2
 Epidemiology
Isolated proteinuria: 1.5 15% in
children on a single urin screen
(asymptomatic proteinuria 0,6
6,3%)

Transient finding does not denote

renal disease: stress (exercise, fever,
dehydration), postural change
 Pathophysiology

Glomerular Tubular
filtration reabsorbtion

Molecular Tubular
weight epithelial
Negative function
charge
Filtration
pressure
Heparan sulfate a proteoglycan (Ext1gene expression) produce by
podocytes is a major contributor of glomerular anionic charge.

molecluar
weight > 40 KD

filtration
pressure
>>>
 Pathophysiology
Glomerular barier disfunction

Glomerular permeability
Loss of negative charge
injury to filtration barier

Tubular epithelial cell disorder

Proximal convoluted tubules damage

Alteration of glomerular blood

flow
Hemodynamic change, intraglomerular
hypertension
 Classification
proteinur
ia

Intermite
persisten
nt/
t
transient

Postural Non-
Non
Glomerular (orthostati postur
glomerular
c) al

Fever,
Primar Second Overfl Secret Tubula exercise,
dehydration
y ary ow ory r , stress,
unknown

Hereditar Acquire
y d
Glomerular proteinuria
Non selective
proteinuria:
Selective proteinuria: leakage of large
protein (IgG)
Leakage of larger
leakage of moderate protein (IgM,
size protein macroglobulin,
Predominance of low fibrinogen) in small
MW protein amount
(albumin, transferin)
 Etiology of glomerular
proteinuria
Congenital / hereditary :
congenital nephrotic syndrome, Alport syndrome

Acquired :
Primary / idiopathic :
minimal change disease, FSGS, MPGN, Ig A nephropathy
Secondary :
Infection : post streptococcal GN, hepatitis B
Multisystem: SLE, HSP, HUS, DM, amyloidosis
Drugs: penicillamine, trimethadione, mercury
Neoplasms : leukemia, lymphoma, carcinoma
Others : kidney-graft rejection, reflux nephropathy,
renal vein thrombosis, renal artery stenosis,
hypertension
 Etiology of tubular
proteinuria
Acquired
Usually proteinuria <
interstitial nephritis
3g/24h
Pyelonephritis
Congenital/ hereditary kidney-graft rejection
Fanconi syndrome acute tubular necrosis
Lowe syndrome Sarcoidosis
Bartter syndrome Nephrocalcinosis:
Renal tubular acidosis Hypercalcemia,Gout
Cystinosis Drugs (analgesics
Polycistic kidney disease papilary necrosis,
Wilson disease aminoglycoside,
cyclosporine)
 Other etiology
Overflow
Secretory proteinuria
Excess Low MW protein Tissue protein excretion
Light chain : (neonate Tamm-Horsfall)
plasma cell dyscrasia UTI mucoprotein
Lysozyme :
Orthostatic
myelocytic leukemia
Increase protein excretion
Myoglobin : in upright position and
rhabdomyolysis normal excretion during
Hemoglobin : recumbency (<
1g/1,73m2/24h)
hemolysis
 Detection of proteinuria

Qualitative
Acetat sodium test (Bang method)

Semi
Urine dipstick
quantitativ
e
Sulfosalicylic acid test

24 h urinary total protein

Quantitati
ve quantification (Esbach)
 Urine dipstick
Excellent screening test able to
detect protein as little as 0.1 0.15
g/L

Colorimetric method Impregnated

with tetrabromphenol blue, buffered
to pH 3,5, binding to protein blue
color proportionate to the amount of
protein present
 Urine dipstick reading

interpretati negati trace + ++ +++ +++

on ve +
concentrati g/L < 0.2 0.3 1.0 3.0 >20
 Quantitative test
24 h urinary total protein
quantification is the most precise
way
May be difficult: very young patient,
enuresis
First morning urine specimen is
recommended for spot urinary
protein: creatinin ratio quantification
 Clinical Approach
Determine: transient, persistent or
orthostatic
History
Nephritic symptoms (edema, hematuria,
polyuria, oliguria) and connective tissue
disorder (rash, joint pain) glomerulonpehritis
Recurent UTI reflux nephropathy
RTI or pyoderma post streptococcal GN
Family history (polycystic kidney, renal failure,
deafness) alport, familial polycystic
 Clinical Approach
Physical examination
Edema, ascites, pleural effusion (SN, GN)
Blood pressure (Acute GN, CKD)
Growth failure, anemia, osteodystrophy (renal
failure)
Increase JVP, hepatomegaly, pulmonary edema
(acute nephritis, renal failure)
Palpable flank mass (hydronephrosis/ polycystic
kidney disease)
Specific sign: rash, palpable purpura, skin
lession (GN)
 Clinical Approach
Laboratory examination
Urinalysis hematuria, pyuria, nitrit
total protein, albumin
hypoalbuminemia
Cholesterol, C3 complement
CBC anemia
BUN, creatinine GFR
Electrolyte
Quantitative protein excretion
 Abnormal Urinalysis in Children:
Proteinuria and Hematuria

HEMATURIA
 Definition
Present of blood in urin
Urine microscopic examination
findings of
RBC > 5/mcL in a fresh uncentrifugated
midstream urine specimen
Fuchs-Roshental method: 10 RBC/mcL
RBC >3/hpf in centrifugated sediment
from 10 ml of freshly voided midstream
urine
Gross (macroscopic) - microscopic
 Differential Diagnosis
Dark yellow or orange
Normal concentrated urine
Drug (rifampicin, warfarin,
pyridium)
Dark brown or black
urine
Bile pigment
Methemoglobinemia
Alanin
Drug (resorcinol, thymol)
Alkaptonuria, tyrosinosis
Red or pink urine
Hemoglobinuria
Myoglobinuria
Porphyrins
Urates (high concentration)
Food (beet, red dragon
fruit)
Drug (benzene, chloroquin,
desferoxamine)
Red smoky dark brown
cola colour urine
Detection
Urine dipstick
Hemoglobin peroxidase
activity convert chromogen
tetramethylbenzidine into Urine microscopy
oxidized form green-blue
colour
Very sensitive, can detect as
little as 150 mcg/L free Hgb
Falseposotive: Fuchs Rosenthal
Hemoglobinuria, chamber
Myoglobinuria, oxidizing
agent (microbial peroxidase- Direct microscopy
UTI)
False negative:
reducing agent (ascorbic
acid, high urine SG)
 Etiology
May originate from glomeruli, renal
tubules or interstitium, urinary tract
(collecting system, ureters, bladder
and urethra)

Practical approach:
systemic vs local
glomerular vs non glomerular
Etiology of hematuria
Glomerular
Familial benign hematuria Non Glomerular
Glomerulonephritis (post- Renal calculi
infectious, HSP, IgA
nephropathy, SLE) Coagulopathy
Hereditary nephritis Malignancy
(Alport syndrom) UTI
Hemolytic uremic
Hypercalciuria
syndrome
Renal vein thrombosis Trauma
Cystic renal disease Menarche
Interstitial nephritis Exercise induced
Vascular malformation
Diagnostic approach:
clinical evaluation
Macroscopic hematuria glomerular origin: brown,
tea colored, cola colored; lower urinary tract: pink or
red
Accompaniying edema and hypertension
glomerulonephritis
Accompaniyng voiding symptomps (frequency,
urgency, disuria, enuresis) non glomerular cause
Systemic symptoms: rash, arthritis secondary GN
History of drug ingestion, preceeding infection
History of sexual activity in pubertal adolescence
Ballotable renal mass or palpable bladder
 Identification of
bleeding source
Three cylinder test urine collection Collect urine
specimen at beginning, in the middle and at the
end of urination in 3 different glass cylinders
observe the urine colour
Initial hematuria: 1st cylinder looks more reddish
bleeding from posterior urethra, meatal stenosis (urethral
origin)
Terminal hematuria: 3rd cylinder looks more reddish
bleeding from the bladder neck or proximal urethra
(bladder cause)
Total hematuria: all cylinders looks reddish
bleeding comes from the kidney or severe bleeding from
bladder (acute hemorrhagic cystitis)
Diagnostic approach:
urine microscopic examintaion
RBC:
false negative when urine is low SG, alkaline pH hemolyzed

WBC:
consider UTI and interstitial/ glomerular inflamatory disorders
Neutrophil: UTI, postinfectious GN
Eosinophil: interstitial nephritis

Cast:
RBC cast suggesting GN, disintegrate rapidly in alkaline urine
granular appearance
Hyalin casts associated with proteinuria
Granular cast glomerular origin

Crystal: urate, calcium oxalate, cystine crystals

 References
Miner JH. Glomerular filtration: the charge debate
charges ahead. Kidney International 2008; 74: 259
61 . doi:10.1038/ki.2008.260

Goldsmith D, Gadsby R, Smith S, Thomas N,

ODonoghue D and Hunter J. Proteinuria and use of
estimated Glomerular Filtration Rate (eGFR). Kidney
Diseases Specialist Library 2008; 27: 915

Yap HK, Lau PYW. Hematuria and proteinuria. In:

Comprehensive Pediatric Nephrology (1st edition). Ed:
Geary DF, Schafer F. Mosby, Elsevier 2008; 17994
Thank
You
dr.kryzt@gmail.com

Division of Pediatric Nephrology

Department of Child Health
Faculty of Medicine, Universitas Gadjah Mada
Sardjito Hospital Yogyakarta
2015