Proteinuria

Department of the Navy
Bureau of Medicine and Surgery

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.

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.

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, NSAID’s, 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.

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 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.