Reduced intrarenal protein degradation as a potential mediator of glomerulosclerosis and tubulo-interstitial fibrosis

Chronic renal failure is the consequence of progressive glomerulosclerosis and tubulo-interstitial fibrosis. The initiating hallmark of nephrosclerosi s represents nephronal hypertrophy, due to an accumulation of proteins in t he glomeruli and tubulointerstitium. From experimental and clinical investigations the conclusion can be drawn t hat the disturbed intrarenal protein balance with the consequent nephronal hypertrophy is at least partly the result of reduced protein degradation. P otential factors involved in impaired renal proteinase activities are cytok ines like transforming growth factor beta(1) (TGF-beta(1)), angiotensin II and advanced glycation endproducts (AGEs). Conclusion: Nephrosclerosis as the common histological endpoint of chronic renal insufficiency is the result of an interaction between many pathogenet ic factors. Its growing understanding implies the possibility of new therap eutic options to retard the progressive course of chronic renal failure.