Clinical perspectives in the prevention and treatment of chronic nephropathy, including an overview of the DEMAND Study

Abstract

Background: The prevalence of chronic renal disease is increasing: 1.8 million people worldwide are affected by end-stage renal disease (ESRD) and need dialysis. Preventing the progression of renal disease is therefore important, particularly in patients with type 2 diabetes mellitus (DM), since the number of diabetic patients requiring dialysis--as well as the relative costs of such treatment--are increasing rapidly. Objective: The goal of this article was to provide a summary of how effective control of systemic blood pressure and proteinuria can slow the progression of ESRD. An overview of the design of the ongoing Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) study is also given. Methods: A literature search of MEDLINE was conducted for the period 1992 through 2005, using the following search terms: diabetes, microalbuminuria, ESRD, hypertension, manidipine, and proteinuria control. Results: Optimal blood pressure and proteinuria control, as well as glycemic and lipid control, are of utmost importance in minimizing the incidence and progression of nephropathy and cardiovascular diseases in patients with type 2 DM. Once overt nephropathy occurs, renal function will decline linearly with time until the patient needs renal replacement therapy, either dialysis or renal transplantation. It should be noted, however, that all patients do not lose renal function at the same rate. Therefore, the aim of treatment is to modify the rate of disease progression from a rapid pattern to a very slow one. The effects of angiotensin-converting enzyme (ACE) inhibitor therapy on proteinuria and the progressive decline in glomerular filtration rate (GFR) in diabetic and nondiabetic patients have been addressed in several trials, including the Ramipril Efficacy in Nephropathy core study. This study showed that at comparable levels of blood pressure control, ACE inhibitors were more effective than conventional antihypertensive treatment at reducing proteinuria, slowing the rate of GFR decline, and limiting the progression of ESRD. The goal of the DEMAND study is to assess the efficacy of the third-generation dihydropyridine calcium channel blocker manidipine, given in association with delapril, an ACE inhibitor, in the treatment of diabetic nephropathy. The results are expected in 2008. Conclusions: The nephroprotective treatment of diabetic patients should start before they develop proteinuria, both to avoid ESRD and to prevent cardiovascular disease. In this respect, the goal of the DEMAND study is to determine if the combined therapy between delapril, an ACE inhibitor, and manidipine, a dihydropyridine calcium channel blocker, slows the rate of GFR decline more effectively than conventional antihypertensive therapy in hypertensive type 2 diabetic patients with normo- or microalbuminuria.