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 albuminuria, an important screening tool for diabetic nephropathy. Urinary albumin excretion between 30 and 300 mg/day (20-200 mcg/min) is called moderately increased albuminuria (formerly known as “microalbuminuria”); albumin excretion >300 mg/d (200 mcg/min) is considered to represent severely increased albuminuria (formerly known as “macroalbuminuria”). The natural history of steadily increasing albuminuria over the years is a key diagnostic feature of diabetic nephropathy.
Formal assessment of urinary protein excretion requires a 24-h urine protein collection (see “Abnormalities of Renal Function, Azotemia Azotemia and Urinary Abnormalities,” 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. 145 Glomerular Diseases). 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 (a viral form of collapsing glomerulopathy).
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. 145 Glomerular Diseases.
Gross hematuria refers to the presence of frank blood in the urine and is more characteristic of lower urinary tract disease and/or bleeding diatheses than intrinsic renal disease (Table 48-3 Major Causes of Hematuria). Cyst rupture in polycystic kidney disease and postpharyngitic flares of IgA nephropathy are exceptions. Microscopic hematuria (>1-2 red blood cells [RBCs] per high-powered field), accompanied by proteinuria, hypertension, and an active urinary sediment (the “nephritic syndrome”) is most likely related to an inflammatory glomerulonephritis, classically poststreptococcal glomerulonephritis (Chap. 145 Glomerular Diseases).
Free hemoglobin and myoglobin are detected by dipstick; a negative urinary sediment with strongly heme-positive dipstick is characteristic of either hemolysis or rhabdomyolysis, which can be differentiated by clinical history and laboratory testing. RBC casts are not a sensitive finding but when seen are highly specific for glomerular bleeding, usually, but not exclusively, caused by glomerular inflammation. Specificity of urinalysis can be enhanced by examining urine with a phase contrast microscope capable of detecting dysmorphic red cells (“acanthocytes”) associated with glomerular disease.
The approach to the pt with hematuria is shown in Fig. 48-3. Approach to the Pt with Hematuria.