Cellular and metabolic consequences of chronic ischemia on kidney function

Approximately 15% of end-stage renal disease is attributable to chronic ischemic nephropathy from renovascular disease, representing significant patient morbidity and sizable medical costs. Although the pathophysiology of both ischemic acute renal failure and renovascular hypertension are under intense study, there have been little data obtained on the pathophysiology of chronic ischemic injury to the kidney. Data from studies of renovascular hypertension demonstrate the primary dependence of the stenotic kidney on angiotensin II in maintenance of glomerular filtration rate, although other vascular regulators, such as endothelium-derived nitric oxide and endothelin, may also play a role. Clues to the pathophysiology of cellular injury in chronic ischemic nephropathy can be found in acute models of ischemic injury to the tubules, toxic models of chronic decreased blood flow such as cyclosporine, and from recent pathological studies showing immunologic alterations. Because there are very little data on the cellular mechanisms of chronic ischemic injury to the kidney, this is an important area for laboratory investigation, particularly because the techniques developed both in studies of acute renal ischemia and chronic renovascular hypertension are readily available. Further understanding of the cellular mechanisms of chronic renal ischemia may eventually lead to medical interventions for patients with ischemic nephropathy too ill to undergo major abdominal surgery.