How high should an ACE inhibitor or angiotensin receptor blocker be dosed in patients with diabetic nephropathy?

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), two drug classes that effectively block the actions of the renin-angiotensin system (RAS), have unique capabilities as antihypertensive agents. Recent landmark clinical trials have demonstrated their important roles as primary therapy for the prevention of renal disease in diabetes. The optimal dosage of these RAS blockers required to slow the progression of renal disease or impair the development of cardiovascular risk is not known. However, data from many studies strongly support the use of the higher doses of ACE inhibitors or ARBs to reduce proteinuria. All studies of kidney disease progression demonstrate benefit on slowing only when blood pressure is reduced when using higher doses. In order to accrue the optimum benefit from ACE inhibitors and ARBs, the dose-response relationship for diabetic renal disease will have to be determined. The best strategy, ie, supramaximal doses of ACE inhibitors or ARBs or combining them, is still a matter of debate but may be resolved soon by results of ongoing studies.