Reduction of proteinuria with angiotensin receptor blockers

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.