Albumin fragments in normal rat urine are derived from rapidly degraded filtered albumin

Filtered albumin is excreted as a heterogeneous population of albumin‐derived molecules resulting from degradation during renal passage. In order to understand the dynamics of this degradation process, albumin clearance was studied over a short‐term (minutes) and a long‐term (7 days) by both radioactivity and radioimmunoassay. The radiolabelled material in the urine was also analysed extensively by using size exclusion chromatography, size selective filtration and high performance liquid chromatography. These studies demonstrate that during renal passage, albumin degradation to fragments in the size range of 500–10 000 occurs in a matter of minutes. The fragments are not detected by using radioimmunoassay. Steady state excretion rates or fractional clearance of radiolabelled albumin occur over a similar time period. Both rates of degradation and approach to steady‐state clearance, while rapid, were considerably slower than the transit time for molecules in the Bowman's capsule and early tubular lumen. The results are consistent with an extremely rapid lysosomal uptake of filtered albumin, and degradation and regurgitation of the albumin‐derived peptide fragments into the tubular lumen prior to excretion.