Mechanisms of injury in progressive renal disease

Recognition that loss of renal function is progressive has led to extensive investigation into risk factors and mechanisms of injury. Persistent activity of the underlying disease contributes, though progression may proceed in its absence. Nephrotoxic insults which pose little threat to the normal kidney may enhance progression in the diseased kidney. Functional adaptations, including glomerular hypertension and proteinuria, in themselves contribute to ongoing destruction. Structural and cellular adaptations, including tubulointerstitial fibrosis, also play a role. A large number of mediators of injury have been identified, as well as dietary and metabolic factors which act through these mediators and mechanisms. This brief overview will summarize the various mechanisms which have been proposed and which are likely to alter clinical strategies to slow the progression of renal disease.