The Renal Protective Effects of Angiotensin II Receptor Blockers in Type 2 Diabetes Mellitus

Coyle JD, Gardner SF, White CM. Ann Pharmacother. 2004;38:1731-1738.

Tight blood pressure control is one of the most important factors for the prevention of renal disease in diabetes. For every 5 mm Hg increase in mean arterial blood pressure, the risk of renal disease has been shown to increase 1.2-fold. Angiotensin II blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are each considered first-line treatment in hypertensive patients with type 2 diabetes to slow the progression of renal disease, as recommended by the American Diabetes Association. Numerous studies have demonstrated the renal protective effect of ARBs—in addition to that attributable to a reduction in blood pressure—in hypertensive patients with type 2 diabetes and microalbuminuria or proteinuria.

Four studies of particular importance are the IRMA-2 study (Irbesartan Microalbuminuria), MARVAL (Microalbuminuria Reduction with Valsartan), IDNT (Irbesartan Diabetic Nephropathy Trial), and RENAAL (Reduction of Endpoints in the NIDDM with the Angiotensin II Antagonist Losartan). In IRMA-2 and MARVAL, the renal protective effects of an ARB in early-stage renal disease were demonstrated. In IDNT and RENAAL, the renal protective effects of an ARB in late-stage renal disease were demonstrated. The renal protective effects of ARBs in normotensive patients with type 2 diabetes with only a small decrease in blood pressure has also been demonstrated in the MARVAL study, suggesting the feasibility of the use of ARBs in such patients.

The results of the IRMA-2 study suggest that the dose of an ARB should be titrated upwards to optimize the reduction in albuminuria/proteinuria and blood pressure, as the dose of ARB required to achieve maximal reduction in proteinuria seems to be higher than that required to achieve maximal blood pressure reduction. Patients with type 2 diabetes and hypertension may require 2 agents for blood pressure control. However, it is not yet known if the addition of a second renal protective agent (ACE inhibitor or nondihydropyridine calcium channel blocker) to a maximal dose of ARB provides greater renal protection than the use of another class of antihypertensive treatment (thiazides or β-blockers).

ARBs play an important role in slowing the progression of renal disease in hypertensive patients with type 2 diabetes, as established by numerous studies. However, further studies of the renal protective benefits of antihypertensive treatments when used in combination are needed.