Beneficial impact on cardiovascular risk factors by dual blockade of the renin-angiotensin system in diabetic nephropathy

Abstract

Background. Patients with diabetic nephropathy have a high risk of cardiovascular disease and end-stage renal disease. Dual blockade of the renin-angiotensin system (RAS) with both ACE inhibitors (ACE-I) and angiotensin II receptor blockers may offer therapeutic advantages. Methods. Based on three double-blind randomized cross-over trials, we analyzed the short-term effects of dual blockade of the RAS on cardiovascular surrogate end points in 51 type 1 diabetic patients with diabetic nephropathy. Results. Compared to ACE-I, dual blockade of the RAS decreased albuminuria 37% from 558 mg/24 hour, and lowered 24-hour blood pressure 7/5 mm Hg from 137/76 mm Hg (P < 0.01). In addition, dual blockade lowered total and LDL-cholesterol 0.3 from 5.4 mmol/L and 3.1 mmol/L, respectively (P ≤ 0.01). The antialbuminuric response to dual blockade of the RAS was influenced by the insertion (I)/deletion (D) polymorphism in the ACE gene. Conclusion. Dual blockade of the RAS may offer additional cardiovascular and renal protection in type 1 diabetic patients with diabetic nephropathy. Determination of the ACE/ID genotype may help identify patients particularly sensitive to such therapy. © 2004 by the International Society of Nephrology.