Angiotensin-converting enzyme inhibition in renal disease; contrasting effects on renal function in renal artery stenosis and progressive renal injury

Abstract

Renal failure is progressive irrespective of the underlying primary renal disease or continued disease activity. Intrarenal haemodynamic changes may contribute to progressive loss of renal function, and may be modified by pharmacological therapies. Angiotensin-converting enzyme (ACE) inhibitors may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. We have studied the effects of an ACE inhibitor and a calcium channel blocker on systemic BP, glomerular filtration, proteinuria and histological injury in animal models of progressive renal disease (the remnant kidney and diabetes). Systemic BP was lowered similarly by each treatment in both models. Beneficial effects on renal structure, proteinuria, and glomerular filtration only occurred in the ACE inhibitor-treated animals. Intrarenal haemodynamic effects of ACE inhibitors may therefore offer an advantage over other antihypertensive agents in progressive renal disease. Where there is reduced renal perfusion, intrarenal haemodynamic effects of ACE inhibitors may lead to compromised renal function. Acute renal failure is a common consequence of ACE inhibitor therapy in patients with bilateral renal artery stenosis, or renal artery stenosis to a single functioning kidney. Acute studies have suggested that these effects are reversible; function returns following withdrawal of ACE inhibitor therapy. We examined the long-term effects of ACE inhibitor therapy in rats with the two-kidney, one-clip (Goldblatt) model of hypertension. Rats were treated for 12 months with an ACE inhibitor or a vasodilator. After 1 year of treatment the clipped kidney from the ACE inhibitor-treated rats was small, fibrotic, and had no glomerular filtration. No functional improvement of the clipped kidney occurred following ACE inhibitor withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)