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Evaluate proteinuria (eg, following urinalysis in which proteinuria is detected); evaluate renal diseases, including proteinuria complicating diabetes mellitus, the nephrotic syndromes (eg, lipoid nephrosis, membranous proliferative glomerulopathies, metal poisoning (eg, gold, lead, and cadmium), renal vein thrombosis, systemic lupus erythematosus (SLE), constrictive pericarditis and amyloidosis); work up other renal diseases including malignant hypertension, glomerulonephritis, Goodpasture syndrome, Henoch-Schönlein purpura, thrombotic thrombocytopenic purpura, collagen diseases, cryoglobulinemia, toxemia of pregnancy, drug nephrotoxicity, hypersensitivity reactions, allergic reactions and renal tubular lesions; manage myeloma and macroglobulinemia of Waldenström (Bence Jones proteinuria); evaluate hypoproteinemia; tubular proteinurias include Wilson's disease and Fanconi syndrome.
Although evaluation for proteinuria may be the best single test to work up chronic renal disease, proteinuria may wax and wane. Toxemia is a state in which urine protein excretion is commonly measured. The standard for most methodologies is albumin. The different methods are more or less sensitive to globulin than to albumin, so far nonselective proteinurias, where a variety of proteins are present, the different methodologies will give different results. Twenty-four hour urine collections are subject to collection errors. The laboratory method, depending on an aliquot and varying dilutions, is subject to calculation errors, which must be carefully guarded against. When protein is determined by precipitation methods, x-ray contrast media, tolbutamide, penicillin or cephalosporin analogs, and sulfonamides may cause false-positives. Pyridium® interferes with the reaction by causing color interference. Functional and postural proteinuria occur.
Normal urine protein consists of albumin (≤35 mg/24 hours), other plasma proteins (ie, globulins, haptoglobin, β2-microglobulin, and light chain). Tamm-Horsfall glycoprotein secreted by renal tubular cells may contribute ≤50 mg/24 hours. Urinary protein in normals tends to increase with age, exercise, and standing posture.
Tests requiring a 24-hour urine collection with no preservative, such as creatinine, may also be performed on the same specimen. Although quantitative protein can be run on a random specimen or timed collections less than 24 hours, 24-hour collections are preferable for evaluation of the nephrotic states and inflammatory renal disorders. Creatinine, creatinine clearance, BUN, serum protein electrophoresis, ANA, anti-DNA antibodies, HIV, hepatitis C antibody, hepatitis B antigen, and complement levels (including total complement, C3, C4) are among useful tests to work up patients with proteinuria. Urine electrophoresis, immunofixation and immunoelectrophoresis are useful in patients older than 35 years of age to investigate possible diagnosis of amyloidosis, myeloma, and Waldenström macroglobulinemia.
Some patients exhibit orthostatic proteinuria (ie, recumbent urine protein 100−180 mg in a 12-hour overnight urine collection and up to 1 g in the subsequent 12 hours while ambulatory). The presence of >200 mg of urinary protein in the overnight specimen or equally increased amounts of urine protein in both specimens indicates a need for further work-up.1
Nephrotic syndromes are the causes of the most severe urinary protein losses. Nephrotic syndrome is defined now usually by degree of proteinuria (ie, proteinuria >50 mg/kg/day). After time, additional signs and symptoms occur including hypoproteinemia, hypoalbuminemia, elevation of α2-globulin with decreased γ-globulin on electrophoresis, hyperlipidemia, and edema. Urinary albumin is a more sensitive marker of progression and regression of renal disease than urine total protein, especially when urine total protein is <300 mg/g creatinine. In most laboratories, urine albumin is available from protein electrophoresis following concentration procedures; however, this method is not sensitive to low concentrations of albumin.2 Albumin, 24-Hour Urine is the preferred test.
1. Glassock RJ. Postural (orthostatic) proteinuria: No cause for concern. N Engl J Med. 1981 Sep 10; 305(11):639-641. PubMed 7266588
2. Shihabi ZK, Konen JC, O'Connor ML. Albuminuria vs urinary total protein for detecting chronic renal disorders. Clin Chem. 1991 May; 37(5):621-624. PubMed 2032314
