• Congenital nephrotic syndrome
• Faconi syndrome
• Congenital syphilis
• Cystinosis

• Viral
  • Hepatitis B, Epstein-Barr virus, cytomegalovirus, HIV
• Bacterial
  • Acute poststreptococcal glomerulonephritis
  • Subacute bacterial endocarditis
  • Urinary tract infections
• Parasitic
  • Malaria
  • Schistosomiasis

• Allergens
  • Pollens, inhalants
• Venoms
  • Bees and snakes
• Immunizations
• Heavy metals
• Heroin
• Medicines
  • Captopril
  • Penicillamine, non-steroidal anti-inflammatory agents, aminoglycosides

• Minimal change nephrotic syndrome
• Hereditary nephritis
• Membranoproliferative glomerulonephritis
• Membranous glomerulonephritis
• Messangial proliferative glomerulonephritis
• Focal segmental glomerulosclerosis
• Henoch-Schönlein syndrome
• IGA nephropathy
• Systemic lupus erythematosus nephritis
• Systemic vasculitides
• Shunt nephritis
• Subacute bacterial endocarditis

• Hypokalemic nephropathy
• Diabetic nephropathy
• Hypothyroidism

• Wilms tumor
• Carcinomas
• Lymphoma
• Leukemia

• Orthostatic proteinuria
• Persistent asymptomatic proteinuria

• Sickle cell disease
• Renal vein thrombosis
• Hemolytic uremic syndrome (HUS)

• Orthostatic proteinuria
• Strenuous exercise
• Fever
• Emotional stress
• Cold exposure
• Congestive heart failure
• Seizure

• Ischemic tubular injury
• Reflux nephropathy
• Interstitial nephritis

Determine the etiology of the proteinuria and determine what therapy there is to possibly treat the problem.

Question: Is there a pre-existing history of renal disease?
Significance: Obviously, in case of proteinuria a prior history of renal disease will allow the physician to a more aggressive approach to the patient. Even the history of nephritis in the past can be important finding in the evaluation.

Question: Is there a history of abnormal screening urinalyses?
Significance: It is common for primary care physicians to use colormetric urine dipstick at well child check-ups. In the case of proteinuria (1+ or greater), it is important to see if there is a previous history of protein in the urine.

Question: Is there a history of previous or multiple urinary tract infections?
Significance: Urinary tract infection can be associated to other renal/urinary tract problems, such as vesico-ureteral reflux, which leads to damage of the kidneys and thus proteinuria.

Question: Is there history of a preceding illness?
Significance: Occasionally, a disease can precede the onset of nephrosis.

Question: Familial history of renal disease, metabolic disease, or mental retardation?
Significance: Some renal diseases are inherited or associated with genetic diseases, which cause mental retardation.

Question: Recent heavy exercise?
Significance: Strenuous exercise can cause a transient proteinuria trace to 1+ on urine dipstick. Follow-up urinalysis without exercise in previous 24 hours or test for orthostatic proteinuria should be done.

Question: Does the child have an unremarkable previous medical history?
Significance: A majority of children will have no significant past medical history for renal disease. Based on data a small percentage of people will have persistent proteinuria on follow testing.

Finding: Hypertension
Significance: Hypertension greater than the 95 percentile for gender and age is important to evaluate for renal disease. Proteinuria and hypertension should quickly alert the primary care physician to focus on a renal etiology.

Finding: Edema (usually dependent and pitting)
Significance: In severe proteinuria, edema may be present in the patient. Edema is the result of third spacing of fluid into the interstitial tissues. In general, the appearance of edema can have intravascular hypovolemic dehydration. Potassium sparing diuretics are usually chosen in hypoproteinemic edema. Loop and thiazidediuretics can exacerbate a patient in the intravascular hypovolemic state (see Nephrotic syndrome).

Finding: Acites/pleural effusion
Significance: The spacing of fluid usually results of fluid in the peritoneal cavity (ascites). The fluid may move into the pleural cavity from the abdominal cavity. This fluid is at risk for secondary infection.

Finding: Shifting dullness in abdomen
Significance: As the patient is rolled from side to side, percussion of the abdomen will show dullness following the shifting of the ascitic fluid.

Finding: Purpura
Significance: Henoch-Schönlein purpura (HSP) can be a reason for renal disease. Purpura is usually on the buttocks, lower extremities, and dependent areas.

Finding: Suprapubic and costovertebral tenderness
Significance: Urinary tract infections or pyelonephritis can be a cause of isolated proteinuria. White blood cells, nitrites, and blood are also present with infection.

Test: Urine colormetric dip stick
Significance: A quick and reliable method to evaluate proteinuria; 1+ or greater should lead a physician to evaluate a patient for etiology of the finding. This test also allows a family member to follow proteinuria at home and notify the physician or changes in a patient’s physiology. If follow-up urines are 100% positive (1+ or greater), the physician should test conduct a 24-hour collection and then consider referral to a nephrologist. See Relationship Between Urine Protein and Dipstick Results.

Relationship Between Urine Protein and Dipstick Results

Test: 24-Hour collection of urine
Significance: After the collection, an analysis of total protein, creatinine, and electrolytes can be studied. In the evaluation of orthostatic proteinuria, the 24-hour collection can be split into standing and recumbent collections. In this case, the overnight, recumbent sample should be less than 100 mg and the rest of the collection should have protein. However, the standing protein can be 2 to 3 times the level of the recumbent. Normal result is less than 4 mg/m² per hour. A pediatric phone consult may necessary to help with the work-up. If the results are greater than 2 g, please see section on nephrotic syndrome. See table 24-Hour Urine Collection Values.

24-Hour Urine Collection Values

Test: Metabolic serum chemistry including blood urea nitrogen (BUN), creatinine, total protein, albumin, and cholesterol
Significance: Renal failure can be identified with a rise in BUN and creatinine nine as well as hyperkalemia. Hypoproteinemia, hypoalbuminemia and hypercholesteremia are seen in nephrotic syndrome (see Nephrotic syndrome).

Test: Urine culture
Significance: In a majority of cases of urinary tract infection, proteinuria can be present. Appropriate antibiotic therapy can treat the infection and in most cases the proteinuria will discontinue. Follow-up urinalysis as well as additional tests should be done if the proteinuria persists.

Test: Additional renal/immunology tests
Significance: Not all the tests are need to evaluate proteinuria, every patient history and physical examination will help determine which tests are needed. They may include an ASO titer, creatinine clearance, urine sediment evaluation by urinalysis, C3, and/or CTXT0 complement level, circulating immune complexes, antinuclear antibody (ANA), hepatitis B surface antigen.

• The person who has unstable vital signs or appears to be septic may need referral. Children with ascites are at risk of peritonitis and can develop complications from spreading of the bacteria. Correction of blood pressure should be done after close evaluation fluid intravascular status is understood. Children can have total body fluid overload and have decreased intracellular fluid. In these casesaggressive diuretic therapy can worsen the patient condition.
• Children with signs of kidney failure, electrolyte abnormalities, non-orthostatic persistent proteinuria, hematuria, hypertension, edema, and or purpura/vasculitis.
• The child with positive familial history of severe renal disease and has developed similar symptoms. Renal biopsy may be needed to be performed by a nephrologist.
• Orthostatic, transient, persistent asymptomatic proteinurias are all diseases that should be followed with serial urine dip analysis and blood pressure measurement. Persistent asymptomatic proteinuria should be followed but many will persist without any additional progression.

• In the routine screening of urine colormetric dip sticks first morning urine are preferable. Because orthostatic proteinurias outlook is common, this is the first test that should be done.
• False-positive proteinuria exists and the usual causes can result from alkaline urine (pH >8), overlong emersions in urine, placing in the direct stream of urine, pyuria, false negatives can exist also in case when the urine is too dilute or a different protein is being excreted other albumin.
• The urine dip stick should be read within 1 minute. After that, the color will become darker and give a false-positive test.
• Trace protein is normal.

Ettenger RB. The evaluation of the child with proteinuria. Pediatr Ann 1994;(23)1:486–494.

Norman ME. An office approach to hematuria and proteinuria. Pediatr Clin North Am 1987;34(30):545–560.