Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study

Diabetic kidney disease is characterized by persistent albuminuria (>300 mg/dl or >200 microg/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.