Introduction
Proteinuria may be the first and only evidence of renal disease. Most healthy
persons excrete up to 150 mg of urinary protein daily, which may vary from negative to 2+
on urine dipstick analysis. Although the prevalence of proteinuria on routine screening of
healthy individuals has been as high as 3.5 percent, the incidence of renal disease in
this population is very low. It is clear that the discovery of proteinuria necessitates a
thorough evaluation to separate these healthy individuals from those with significant
renal disease.
Urinalysis
The reagent strip method (dipstick) is the most commonly employed method to test
for proteinuria. It tests mainly for albumin, is sensitive to 10-30 mg/dl and is read out
by a color change. The intensity of the color change is proportional to the concentration
of protein, with trace = 10-30 mg/dl, 1 + = 30 mg/dl, 2 + = 100 mg/dl, 3 + = 500 mg/dl,
and 4 + >1000 mg/dl. Highly concentrated or alkaline (pH>8) specimens may give a
false positive reaction, while very dilute urine and globulins may give a false negative
reaction.
Evaluation
Once proteinuria is detected by dipstick, the next step should be to obtain a
detailed history, physical exam, and urine microscopy. This includes family history as
well as prior evaluations and medications (i.e., NSAIDs). The exam should look for
evidence of renal or systemic disease, focusing on blood pressure, pulse, fundi,
cardiovascular, skin, abdominal (palpable kidneys or bruits), and the presence or absence
of edema.
Functional Proteinuria
If no such evidence is found, repeat dipstick analysis should be done two or three
times. If these subsequent qualitative tests, in well-concentrated specimens, are negative
for protein, the initial proteinuria is transient or functional. Functional proteinuria
may be seen in conditions such as high fever, emotional stress, cold exposure, strenuous
exercise, infection, and other acute medical illnesses. Idiopathic transient proteinuria
is a common cause of proteinuria in young adults, especially men. It is characterized by
proteinuria on a routine urinalysis that disappears on repeat testing and is found in
asymptomatic, healthy individuals with normal renal function.
Orthostatic Proteinuria
Another entity seen in adolescents (rarely > 30 years) is orthostatic
proteinuria. This type of proteinuria increases in the upright posture. A simple
evaluation follows. The patient voids in the evening and then retires immediately. The
next morning a urine sample is obtained while still supine. The patient then ambulates and
a third sample is obtained. The orthostatic proteinuria will be present in the first and
last specimens and absent in the supine sample.
Higher levels of proteinuria
Higher grades of proteinuria are associated with other conditions as well, such as
diabetic nephropathy, amyloidosis, lymphoma, lupus, NSAIDs, AIDS, myeloma, or
idiopathic glomerulonephritis. Evidence of greater than 3.5 grams of proteinuria per day,
edema, hypoalbuminemia, and hyperlipdemia defines the nephrotic syndrome. Certainly any
individual with a suspect history, abnormal physical exam, lab evaluations, abnormal urine
microscopy, or proteinuria other than obvious functional proteinuria, should be referred
to internal medicine or nephrology for further evaluation.
24 hour urine testing and other lab studies
Collection of a 24-hour urine sample for protein and creatinine is helpful before
consultation. Other lab studies indicated include determination of creatinine
clearance,
serum protein electrophoresis, serum total
cholesterol, and renal ultrasound. In selected
cases, complement levels, ANA, cryoglobulin, hepatitis serology
studies, HIV, and RPR
should be ordered. Renal biopsy is indicated for the differential diagnosis in most cases
of Nephrotic syndrome or other atypical cases, even with lesser amounts of proteinuria.
Treatment recommendations
Treatment of those with significant proteinuria and Nephrotic syndrome will be
instituted by the specialist and may include dietary sodium restriction, diuretics, ACE
inhibitors, corticosteroids and/or cytotoxic agents.
Reviewed by CDR Paul J. Pontier, MC, USNR, Nephrology, Naval Medical Center
Portsmouth, Portsmouth, VA (1999).