The mechanisms of proteinuria in aging rats.

Aging is associated with the appearance of a selective proteinuria which cannot be attributed to any specific underlying renal disease. The present studies were conducted in conscious, chronically catheterized young (3-4 months), non-proteinuric male rats and old (22-25 months), proteinuric males to determine the mechanism(s) of the proteinuria. Compared with young males, old proteinuric rats had increased blood pressure, reduced glomerular filtration rate (GFR) and renal plasma flow and heavy proteinuria. Fractional clearance of neutral dextran (D) and anionic dextran sulfate (DS) were both significantly increased at the 36 A molecular radius in old rats; the increase in DS fractional clearance being greater than the increase in D fractional clearance. The proteinuria of aging is therefore due to moderate increases in glomerular permeability and, more importantly, to loss of fixed glomerular polyanion. Striking glomerular morphologic changes were also evident in the old rats including thickening of the glomerular basement membrane and extensive glomerular sclerosis.