Effect of renal disease on glomerular proteinases.

Until now, little is known about the self-perpetuating mechanism leading to terminal renal failure in chronic renal disease. The common pathological feature of progressive renal insufficiency is focal and segmental glomerulosclerosis. The experimental counterpart of this process is represented by models of streptozotocin diabetes, Adriamycin nephropathy and Goldblatt hypertension. The main initiating hallmark of glomerulosclerosis is an accumulation of glomerular proteins, whose balance is apparently influenced by the activity of glomerular proteinases. In isolated glomeruli of kidneys from experimental animals, total proteinase activity was assayed with an unspecific but sensitive azocasein assay. The activity was significantly reduced in all experimental models at acid and neutral pH when relating enzyme activity to the glomerular protein and DNA content. The demonstration of reduced glomerular proteinase activity in the animal models of glomerulosclerosis could represent a new additional common pathogenetic mechanism. Glomerular protein accumulation could be a result of a synergistic interaction between hemodynamic and biochemical factors; we suggest the latter to be a decrease in glomerular proteinase activity.