Assessment of Dual Blockade of the Renin-Angiotensin System in Patients with. Type II Diabetic Nephropathy

Abstract

With the growmg population of type 2 diabetes, the prevalence of diabetic nephropathy IS nsmg with subsequent increase in ESRD. and heightened risk of cardiovascular mortality and morbidity. This necessitates an urgent need to find better strategies for prevention and management of diabetic nephropathy. The role of the RAS in pathogenesis of diabetes complication, particularly nephropathy, by the impact of its effector molecule, the angiotensin II, is more clearly revealed. Hence, to date, one of the most powerful strategies for ON treatment relies on RAS inhibition with implementation of either angiotensin converting enzyme inhibitors or angiotensin receptor blockers. However either agent does not offer complete blockade of the RAS, and thus is not effective enough to completely prevent the progression of the disease and the development of ESRD. It was proposed that dual blocking of the RAS by the combination of the two classes will offer a superior renoprotection by the complementary effects at different sites.

The present study evaluated the concept of the superior effect of the dual blockade of the RAS by the combination of the angiotensin converting enzyme inhibitor captopril and the angiotensin receptor blocker candesartan compared to captopril alone in Egyptian diabetic nephropathy patients.

• In a crossover randomized design of eight weeks for each intervention, twenty four eligible type 2 diabetes patients with proteinuria> 0.5 g/24 hr and hypertension were

assigned to receive either the combination of captopril 25 mg three times daily and candesartan 16 mg once daily followed by captopril alone, or captopril alone followed by the combination treatment.

Evaluation parameters were recorded at baseline, where all patients withdrawn their antihypertensive medications for two weeks, and at the end of each of treatment period thereafter. These parameters included: Measurement of systolic/diastolic blood pressure, 24 hr urinary creatinine excretion, creatinine clearance based on 24 urine collections, proteinuria assessed either as 24 hr urinary protein excretion or protein