R E V I E W Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study Prasad Bichu1 Ravi Nistala1 Asma Khan2 James R Sowers2 Adam Whaley-Connell1 1Divisions of Nephrology and Endocrinology; 2Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia Missouri, USA Correspondence: Adam Whaley-Connell University of Missouri-Columbia School of Medicine, Department of Internal Medicine, Division of Nephrology CE417, DC043.0 Five, Hospital Dr Columbia, MO 65212 Tel (573)882-7992 Fax (573)884-4820 Email whaleyconnella@health.missouri.edu Abstract: Diabetic kidney disease is characterized by persistent albuminuria ( 300 mg/dl or 200 μg/min) that is conﬁrmed on at least 2 occasions 3 to 6 months apart, with a progressive decline in the glomerular ﬁltration rate (GFR), elevated arterial blood pressure, and an increased risk for cardiovascular morbidity and mortality. Diabetic kidney disease is the leading cause of end stage renal disease (ESRD) prompting investigators to evaluate mechanisms by which to slow disease progression. One such mechanism is to block the activity of angiotensin II at the receptor site and agents that follow this mechanism are referred to as angiotensin receptor blockers (ARB). There is sufﬁcient clinical evidence to support that ARB have protective effects on kidney function in patients with diabetes and hypertension. However, in the past decade there have been few investigations comparing individual ARBs on renal outcomes. Telmisartan, a lipophilic ARB with a long half-life, has been hypothesized to have a greater anti-proteinuric effect when compared to the shorter acting losartan. Therefore, the A comparison of telMisartan versus losArtan in hypertensive type 2 DiabEtic patients with Overt nephropathy (AMADEO) trial sought to investigate renal and cardiovascular endpoints. In this review, we discuss the pathophysiology of diabetic kidney disease and implications of the AMADEO trial in the context of current understanding from recent outcome trials. Keywords: diabetic kidney disease, hypertension, telmisartan, AMADEO Introduction Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD)1 and is a multifactorial combination of hemodynamic and metabolic abnormalities that collectively contribute to kidney damage resulting in proteinuria and reductions in glomerular ﬁltration rate (GFR). Recent data support that proteinuria is a surrogate maker for cardiovascular risk and reductions in proteinuria correlate with declines in cardiovascular morbidity and mortality. Thereby, interventions that target blood pres- sure control and proteinuria, speciﬁcally interruption of the renin-angiotensin system (RAS) with either angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB), have been utilized in attenuating the progression of DKD.2 Among available ARBs, telmisartan has been reported to have a greater lipophilic- ity, longer half-life, and debatably the most consistent reductions in blood pressure. Therefore, investigators recently sought to compare telmisartan with losartan, which has less lipophilicity and a shorter duration of action, in patients who had overt DKD (urinary protein to creatinine ratio 700) in the A comparison of telMisartan versus losArtan in hypertensive type 2 DiabEtic patients with Overt nephropathy (AMADEO) trial. Investigators reported that telmisartan was superior to losartan in reducing proteinuria in hypertensive patients with DKD with relatively similar reductions in blood pressures. Further, the authors proposed that the superiority of telmisartan could Vascular Health and Risk Management 2009:5 129–140 © 2009 Bichu et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 129