Last updated: October 10, 2014
Description: Quantitative tests for proteinuria are commonly performed. Normal persons may secrete approximately 150 mg of protein into the urine in a 24-hour period. Albumin constitutes only a fraction of this (15–40 mg); the remainder is composed of many different proteins derived predominantly from the renal cells. The most prevalent of these is the Tamm-Horsfall mucoprotein derived from the loop of Henle, which is made in amounts of as much as 50 mg/day. Increased amounts of protein in the urine result most commonly from glomerular damage that allows plasma proteins to enter the urine.
Method: Proteinuria is initially screened for by dipstick testing. This colorimetric chemical reaction depends on urine protein concentration rather than absolute amount. Thus, results may vary considerably depending on how concentrated the urine is. The test is semiquantitative, with results typically reported as 0, trace, + (or 30 mg/dL), ++ (or 100 mg/dL), and +++ (or >300 mg/dL). Proteinuria can be better quantified with a 24-hour urine collection. A close estimate of 24-hour protein excretion may also be obtained from a single (“spot”) urine sample if the amount of protein is correlated with the concentration of creatinine in the same sample. This gives an estimate of the amount that would be excreted in 24 hours.
Individual proteins in a urine sample may be determined by protein electrophoresis (similar to SPEP, see Serum Protein Electrophoresis). This distinguishes proteinuria reflecting glomerular injury (largely albumin) from tubular proteinuria (diverse proteins that migrate in the α, β, and γ regions) from proteinuria related to myeloma (proteins that typically migrate in the -y region). The specific type of immunoglobulin in the urine may be identified by immunoelectrophoresis. Patients with diabetes mellitus often secrete increasing amounts of albumin in their urine as the disease progresses. Albumin present in the urine in the early stages of diabetes is often missed by dipstick. Microalbuminuria can be detected by several test reagents now available that allow detection of concentrations as low as 5 mg/dL.
Normal Values: Normally, approximately 150 mg of protein is excreted into the urine in a 24-hour period. Amounts >500 mg/day are often considered clinically significant. Excretion of >3.5 g of protein is considered massive proteinuria. Massive proteinuria associated with hypoalbuminemia, edema, and hyperlipidemia is known as the nephrotic syndrome.
Increased in: Proteinuria may be seen in a variety of conditions (Table 15).
Confounding Factors: Dipstick analysis of urine for protein is most sensitive to albumin, so substantial amounts of other proteins may be missed. Because dipstick urinalysis is so dependent on protein concentration, significant amounts of excreted protein may be missed in a dilute urine sample. Analysis of a concentrated early morning urine specimen is one way to address this problem. The common assumption that microhematuria itself causes proteinuria is usually false; 1 mL of blood contains 5 million red blood cells but only 70 mg of protein. When diluted in urine, this usually falls below the level of detection for proteinuria. Thus, proteinuria in the setting of microhematuria (as opposed to massive hematuria) usually reflects glomerular damage. Last, some drugs may cause false-positive dipstick results (e.g., tolbutamide, chlorpromazine, high-dose penicillin, sulfonamide, cephalosporin, iodine contrast).
|Table 15: Causes of Proteinuria
|Minimal change disease|
|Mesangial proliferative glomerulonephritis (e.g., IgA nephropathy)|
|Focal segmental glomerulonephritis/glomerulosclerosis|
|Glomerular disease associated with systemic conditions|
|Systemic lupus erythematosus (lupus nephritis)|
|Granulomatosus with polyangiitis|
|Subacute bacterial endocarditis|
|Human immunodeficiency virus|
|Proteinuria associated with drugs|
|Intramuscular gold salts|
|Benign proteinuria (typically <2.0 g/d)|
Indications: Determination of proteinuria is useful in a number of diseases. In rheumatology, it is most commonly used to determine the extent of glomerular injury from diseases such as SLE or drugs such as gold (Table 15).
Cost: Urinalysis, $14–26; 24-hour urine protein quantification, $60–80.