Renal Pathophysiology



would be detected with a total protein determination or a urinary immuno electrophoresis. An older bedside test using sulfosalicylic acid added to the urine supernatant will detect all proteins, with the degree of turbidity noted being proportional to the protein concentration. What factor other than the rate of albumin excretion will affect the urine albumin concentration and therefore the intensity of the reaction on the urine dipstick? What else may be measured in the urine to correct for these variables? Normal Values and Quantitation Normal subjects usually excrete between 40 and 80 mg of protein per day, with the upper range of normal being 150 mg/day. A number of different pro teins are excreted. Albumin, for example, accounts for < 20 mg/day, whereas Tamm-Horsfall mucoprotein (THMP, uromodulin) accounts for 30 to 50 mg/day. The latter is a protein of uncertain function that may have an immunomod ulatory role in preventing the development of urinary tract infections and kidney stones. The protein is secreted by the cells in the thick ascending limb of the loop of Henle, and it constitutes the matrix for almost all urinary casts. Mutations in THMP result in two autosomal-dominant disorders: typical fa milial juvenile hyperuricemic nephropathy and type 2 medullary cystic kid ney disease. Both disorders are characterized by hyperuricemia, medullary cysts, interstitial nephritis, and progressive renal failure. Daily protein excretion has traditionally been measured by a 24-hour urine collection (the gold standard). There is, however, a much more con venient alternative to estimate the degree of proteinuria: calculation of the ratio of total protein to creatinine (in mg/mg) on a random urine specimen. By normalizing the protein concentration to the amount of creatinine in a random sample, variations in urine protein concentration (due to variable oral intake) are avoided. The fortuitous observation that the average daily creatinine excretion is ∼ 1,000 mg/day permits the ratio to approximate the 24-hour protein excretion rate. If, for example, a random urine specimen con tains 210 mg/dL of protein and the creatinine concentration is 42 mg/dL, then the patient is excreting ∼ 5 g/day/1.73 m 2 (210 ÷ 42 = 5). Figure 8.1 shows that there is a good correlation between random urine protein/creatinine ratios and 24-hour determinations. Microalbuminuria The dipstick is relatively insensitive to initial increases in glomerular perme ability because it will not begin to be positive until protein excretion exceeds 300 to 500 mg/day. This is a particular problem in patients with diabetes be cause advanced glomerular injury will already be present by this time. An al ternative that allows much earlier detection of glomerular injury is the direct 1

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