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

Abstract

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.

Diabetic Nephropathy: Diagnosis, Prevention, and Treatment

“…The antiproteinuric effect of ARBs has certain characteristics. It occurs early (within 7 days) after treatment is started and persists stable thereafter (131), and it is independent of blood pressure reduction (116) and has a doseresponse effect beyond the doses needed to control blood pressure (132). An acute increase in serum creatinine of up to 30 -35%, stabilizing after 2 months, might occur in proteinuric patients with creatinine values Ͼ1.4 mg/dl starting ACE inhibitors.…”

Efficacy of drugs in controlling microalbuminuria of diabetic nephropathy

“…The non-superiority of either drug could be due to the fi xed dose used -that is no titration to the maximum tolerated dose. 12 Two subjects on ramipril developed dry cough as an adverse effect, but there were no drop outs. No adverse effect was reported in the losartan group.…”

Drug and Diabetic Nephropathy

“…In subjects with microalbuminuria, the dose of ARBs or ACE inhibitors should be titrated by the clinician until normoalbuminuria is induced, even if supramaximal doses or a combination of ARBs and ACE inhibitors are necessary. There is evidence that achieving reduction in both microalbuminuria and in heavy proteinuria at greater doses than those used to control BP may be required using monotherapy or a combination of these RAS blockers 132 .…”