Fractional clearance of albumin is influenced by its degradation during renal passage.

1. The fractional clearance of intact albumin as determined by fractionation of urine by gel chromatography gave a value of 3.9 +/- 1.6 x 10(-4) for the isolated perfused kidney and 2.1 +/- 0.6 x 10(-4) in vivo using ALZET osmotic pumps. 2. Albumin fractional clearance as measured by detection of the tritium label on the albumin molecule by radioactivity analysis gave a value of 7.5 +/- 3.9 x 10(-3) for the isolated perfused kidney and 2.3 +/- 0.9 x 10(-3) in vivo. 3. The major differences between assays that detect intact albumin compared with non-specific assays in the estimates of the fractional clearance of albumin can be explained by the degradation of approx. 90% of albumin to small peptides during its renal passage. This has been demonstrated by size exclusion chromatography of urine samples from experiments where (i) exogenous tritium-labelled albumin was used in isolated perfused kidneys, (ii) exogenous tritium-labelled albumin was administered intravenously and (iii) analysis was made with metabolically labelled endogenous albumin in vivo.