The child with protein in their urine is a common finding in pediatric practice. Protein may be found in the urine of healthy children. The incidence increases with age and the majority of protein is albumin. 

Mechanisms of Proteinuria

  1. Increased glomerular filtration. The protein must pass through the glomerular capillary wall.
    1. Nephrotic Syndrome- minimal change disease and focal glomerulosclerosis
    2. Glomerulonephritis
    3. Drugs
  2. Decreased tubular reabsorption. Most filtered protein is reabsorbed proximally. With tubular damage, there will be increased protein in the urine
    1. Transport defects- Fanconi's Syndrome, Cystinosis
    2. Toxins- Penicillins, Heavy metals, Aminoglycosides, old tetracycline
    3. Ischemic injury- shock, ATN, Endotoxemia
    4. Obstructive uropathy, Polycystic disease
    5. Increased secretion- normally some protein is secreted but may increase with exercise, acute renal failure, transplant rejection, and stones.

Detection of Protein in the Urine

  1. Dipsticks- Very sensitive and changes color secondary to reaction of tetrabromophenol with amino acids. Have false positives with ph >8, concentrated urine, long immersion time, or presence of wbcs or bacteria. Reading of 1+ needs to rechecked and if continues positive, timed collections should be done.
  2. Timed Collection- technically may be difficult. Doesn't allow for diurnal variations and effect of activity on proteinuria. In adults, >150 mg. 24 hours is positive. In children, > 4 mg./metered squared/hour is positive.
  3. Protein/Creatinine ratio.-Helpful screening tool if timed collection is difficult. Use a randomly collected urine in an ambulating patient. < .5 in less than 2 year old, <.2 in older child. > 3 is in the nephrotic range

Evaluation of Proteinuria


  1. Family history 
  2. UTI symptoms
  3. Drug exposure
  4. Growth history
  5. Recent infections
  6. Hepatitis B status and HIV risk factors
  7. Rashes
  8. joint symptoms

Physical Examination

  1. Edema
  2. Blood pressure
  3. Skin examination
  4. Joints
  5. Chronically ill appearing

If there is repeated >1+ protein on a dipstick, in the absence of significant history, physical findings, and hematuria, a supine urine should be collected. The child should empty their bladder before going to sleep and the first morning urine, while still supine, should be collected. If this is free of protein, another urine should be tested while the child is up and about. If this is positive, the diagnosis of orthostatic proteinuria may be made. The child should have this test repeated a few times over the next year. If both specimens contain protein, further evaluation should be done including:

  1. BUN, Creatinine, and Electrolytes
  2. Complement levels
  3. ASO titers and Lupus serology (if glomerulnephritis suspected)
  4. Nephrology consult

Non-pathological causes of proteinuria

  1. Exercise- should recheck after a few days of inactivity
  2. Fever- recheck when the child is afebrile
  3. Postural or orthostatic proteinuria- very common especially in adolescence. Picked up on routine screen and patient is asymptomatic, the physical examination including BP is normal, and there is no red blood cells in the urine.

Urine is rarely completely free of protein, but the average excretion <150 mg/d

Higher in neonates due to reduce reabsorption of filtered proteins

Protein excretion limited by:

  1. filtration restricted by glomerular capillary wall
  2. reabsorption by proximal tubule

Usually measured via 24-hour urine collection

Functional proteinuria

Benign process stemming from stressors such as acute illness, exercise, and “orthostatic proteinuria”

Overload proteinuria

 Can result from overproduction of circulating, filterable plasma proteins

  •  Multiple Myeloma à Bence Jones proteinuria
  • Rhabdomyolysis à myoglobinuria
  • Hemolysis à hemoglobinuria

Glomerular proteinuria

Nephrotic Syndrome

Glomerular disorder characterized by proteinuria (>3.5g/d) resulting in:

  • Hypoalbuminemia and edema

Often, first manifest as periorbital swelling

  • Hypogammaglobulinemia (loss of Ig) à increased risk of infection
  • Hypercoagulable state (loss of ATIII)
  • Hyperlipidemia and hypercholesterolemia

Minimal Change Disease

 Most common cause of nephrotic syndrome in the pediatric population

Selective proteinuria (loss of albumin, but not Ig)

Typically presents between 2 and 6 years old, boys > girls

Cause is not well understood

May be triggered by recent infection or immune stimulus

May be associated with Hodgkin lymphoma

Clinical findings:

Periorbital swelling and oliguria
Often complain of vague malaise or abdominal pain

If severe, hypotension (third-spacing of volume) and dyspnea (pleural effusion)

H&E: Normal glomeruli

EM: Effacement of foot processes

IF: n/a

Rx: Corticosteroids

Focal Segmental Glomerular Sclerosis (FSGS)

Most common cause of nephrotic syndrome in Hispanics and African Americans

Cause is not well understood

May be associated with HIV, heroin use, and sickle cell disease

H&E: focal and segmental sclerosis
EM: effacement of foot processes
IF: n/a
Rx: poor response to corticosteroids; progression to CRF

Cyclosporine A, Tacrolimus, Rituximab have also been tried

Membranous Nephropathy/Glomerulonephritis
Most common cause of nephrotic syndrome in Caucasians
Occurs more often in older children and adults

May be associated with hepatitis B or C, solid tumors, SLE, or drugs (e.g. NSAIDs, penicillamine)

H&E: diffuse capillary and GBM thickening

EM: “spike and dome” appearance with subepithelial edposits

IF: granular (immune complex deposits)

Rx: poor response to corticosteroids; progression to CRF

Membranoproliferative Glomerulopathy

IF: granular (immune complex deposition)

Type 1: subendothelial (immune complex) deposits

associated with hepatitis B and C

EM: “tram-track” appearance (mesangial ingrowth splits GBM)

Type 2: intramembranous (immune complex) deposits

associated with C3 nephritic factor
EM: “dense deposits”

Rx: poor response to corticosteroids: progression to CRF

Nephritic Syndrome

Inflammation of glomeruli, resulting in hematuria and RBC casts

Also, azotemia, oliguria, hypertension and periorbital edema, and proteinuria (< 3.5 g/d)

Acute poststreptococcal glomerulonephritis (APSGN)

Occurs 2-3 weeks after Group A b hemolytic streptococcal infection of either the skin or pharynx

Usually seen in children, but may occur in adults
H&E: hypercellular, inflamed glomeruli
EM: subepithelial “humps” on EM

IF: granular

Rx: supportive

Children rarely progress to RF

Rapidly Progressive Glomerulonephritis

Progression to RF in weeks to months
H&E: crescents in Bowman’s space
Goodpasture Syndrome

Ab against collagen in glomerular and alveolar basement membranes

Classically in young, adult males

IF: linear

IgA Nephropathy (Berger disease)

IgA immune complex deposition in glomerular mesangium
Most common nephropathy worldwide

Episodes of gross or microscopic hematuria with RBC casts

Beginning in childhood

Usually following URI or acute gastroenteritis (­IgA)

IF: IgA immune complex deposition
May slowly progress to RF

Alport Syndrome

X-linked inherited defect in type IV collagen                                    Results in thinning and splitting of GBM

Presents as isolated hematuria, sensory hearing loss, and ocular disturbances


Occurs as a result of faulty reabsorption of normally filtered proteins (e.g. b2-microglobulin, Ig light chain) in the proximal tubule

Acute tubular necrosis

Injury and necrosis of tubular epithelial cells

Etiology may be ischemic (e.g. sepsis) or nephrotoxic (e.g. aminoglycoside, lead, radiocontrast dye, urate/tumor lysis syndrome)

Brown, granular casts are seen in the urine

Tubulointerstitial nephritis

May be due to drugs (e.g. penicillin, NSAID, sulfa drugs) or viral or bacterial infection

Pyuria (eosinophils) and azotemia

Other symptoms may include: fever, rash, hematuria, CVA tenderness

Fanconi Syndrome

Disorders of the kidney tubules in which certain substances are not reabsorbed

Common causes in children include genetic defects that affect the body’s ability to break down certain compounds:

  • Cystine (Cystinosis) – most common
  • Fructose (Fructose intolerance)
  • Galactose (Galactosemia)
  • Glycogen (Glycogen storage disease)

Other causes in children include:

  • Exposure to heavy metals (e.g. lead, mercury, cadmium)
  • Lowe’s disease (Oculocerebrorenal Dystrophy)
    • X-linked recessive inherited mutation in OCRL gene

Triad: congenital cataracts + neonatal hypotonia with subsequent mental impairment + renal tubular dysfunction

  • Wilson’s disease
  • AR inherited mutation of AP7B (chrom 13)
  • Inadequate hepatic copper excretion
  • Copper accumulates in liver, brain, cornea, kidney, and joints


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  2. Cruz, Carmina and Spitzer, Adrian. When you find protein or blood in the urine. Contemporary Pediatrics. September 1998.
  3. Mahan JD, Turman MA and Mentser MI. Evaluation of Hematuria, Proteinuria and Hypertension in Adolescents. Pediatric Clinics of North America. 1997; 44(6):1573-1589.
  4. Hogg.,R  Evaluation and Management of Proteinuria and Nephrotic Syndrome. Pediatrics June 2000