Biochemical and physiological processes that underlie the mechanism of albuminuria are completely reassessed in this article in view of recent discoveries that filtered proteins undergo rapid degradation during renal passage and the resulting excreted peptide fragments are not detected by conventional urine protein assays. This means that filtered protein and/or albumin levels in urine have been seriously underestimated. The concept that albuminuria is a result of changes in glomerular permeability is questioned in light of these findings and also in terms of a critical examination of charge selectivity, shunts, or large-pore formation and hemodynamic effects. The glomerulus appears to function merely in terms of size selectivity alone, and for albumin, this does not change significantly in disease states. Intensive albumin processing by a living kidney occurs through cellular processes distal to the glomerular basement membrane. Failure of this cellular processing primarily leads to albuminuria. This review brings together recent data about urinary albumin clearance and current knowledge of receptors known to process albumin in both health and disease states. We conclude with a discussion of topical and controversial issues associated with the proposed new understanding of renal handling of albumin.
Copyright 2002 by the National Kidney Foundation, Inc.