This is the hallmark of glomerular disease. Levels up to 150 mg/d are considered within normal limits. Typical measurements are semiquantitative, using a moderately sensitive dipstick that estimates protein concentration; therefore, the degree of hydration may influence the dipstick protein determination. Most commercially available urine dipsticks detect albumin and do not detect smaller proteins, such as light chains, that require testing with sulfosalicylic acid. More sensitive assays can in turn be used to detect microalbuminuria, an important screening tool for diabetic nephropathy. A urine albumin to creatinine ratio >30 mg/g defines the presence of microalbuminuria.

Formal assessment of urinary protein excretion requires a 24-h urine protein collection (see “Abnormalities of Renal Function, Azotemia,” above). The ratio of protein to creatinine in a random, “spot” urine can also provide a rough estimate of protein excretion; e.g., a protein/creatinine ratio of 3.0 correlates to ~3.0 g of proteinuria per day.

Urinary protein excretion rates between 500 mg/d and 3 g/d are nonspecific and can be seen in a variety of renal diseases (including hypertensive nephrosclerosis, interstitial nephritis, vascular disease, and other primary renal diseases with little or no glomerular involvement). Transient, lesser degrees of proteinuria (500 mg/d-1.5 g/d) may be seen after vigorous exercise, changes in body position, fever, or congestive heart failure. Protein excretion rates >3 g/d are termed nephrotic range proteinuria in that they may be accompanied by hypoalbuminemia, hypercholesterolemia, and edema (the nephrotic syndrome). Nephrotic syndrome can be associated with a variety of extrarenal complications (Chap. 141. Renal Transplantation). Massive degrees of proteinuria (>10 g/d) can be seen with minimal change disease, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy, diabetic nephropathy, collapsing glomerulopathy (a subtype of primary FSGS), and HIV-associated nephropathy.

Pharmacologic inhibition of ACE or blockade of angiotensin II should be employed to reduce proteinuria; successful reduction of proteinuria decreases the rate of progression to end-stage renal disease in diabetic nephropathy and other glomerulopathies. Specific therapy for a variety of causes of nephrotic syndrome is discussed in Chap. 141. Renal Transplantation.