Detection of protein on routine urinalysis is a common finding. Its presence may be a benign condition or may be an ominous sign of renal parenchymal disease and renal failure. Therefore, the practitioner should be aware of the differential and follow a logical sequence to differentiate among the different etiologies.

In the normal kidney, the glomerular basement membrane allows for the passage of small molecules into the renal tubule while restricting the passage of macromolecules. Normal protein excretion is affected by the permeability of the glomerular basement membrane and tubular reabsorption mechanisms. Injury to the kidney that increases the permeability or decreases tubular reabsorption will result in increased loss of protein. Glomerular injury results in the loss of intermediate-weight proteins (i.e., albumin) and larger macromolecules. Tubular injury results in increased excretion of low molecular weight proteins secondary to decreased reabsorption.

The upper limit of daily protein excretion is 100 mg/m²day. In adults the limit of normal protein excretion is defined as 150 mg/day. Approximately half of the protein that is excreted originates from the plasma, with albumin representing the largest fraction. The upper limit of albumin excretion is 30 mg/day.

Proteinuria is detected by several methods. The most common test is the urine dipstick. The urine dipstick can only measure the concentration of albumin and can not quantify the amount of protein excreted. The dipstick commonly is reported as negative, trace, 1+ (approximately 30 mg/dL), 2+ (approximately 100 mg/dL), 3+ (approximately 300 mg/dL), and 4+ (approximately 2,000 mg/dL). In contrast, the sulfosalicylic acid test can detect the concentration of all proteins in the urine.

A quantitative measurement of urine protein excretion can be obtained via a 24-hour urine collection. A semiquantitative measurement can be obtained by a urine protein/creatinine ratio. Urinary protein excretion >100 mg/m²/day or a urine protein/creatinine of 0.5 protein/mg in children younger than 2 years of age, or 0.2 mg protein/mg in children older than 2 years of age is abnormal. A urine protein/creatinine ration >3 is suggestive
of nephrotic range proteinuria. Nephrotic range proteinuria is defined as >1,000 mg/m²/day.