Valsartan and the kidney: Present and future

Angotensin (Ang) II type 1 (AT(1)) receptor antagonists are orally active d rugs that specifically block the subtype 1 of Ang receptors. In contrast to AT(1) receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors block the actions of Ang II incompletely. Furthermore, the bradykinin-pote ntiating effects of ACE inhibitors may contribute to the mechanism of actio n of ACE inhibitors. Data in experimental animals suggest that AT(1) recept or antagonists decrease the glomerular filtration rate (GFR) to a lesser de gree than ACE inhibitors. The greater effect of ACE inhibitors in decreasin g glomerular pressure was attenuated with a bradykinin antagonist. In rat m odels of renal damage with proteinuria, acute reduction of proteinuria was seen with ACE inhibitors but not with AT(1) receptor antagonists, whereas l ong-term reductions of proteinuria were of similar magnitude with both agen ts. Renal histology after several months revealed that AT(1) receptor antag onists and ACE inhibitors were equally renoprotective in various renal dama ge models. AT(1) receptor antagonists, like ACE inhibitors, exhibit a natri uretic effect equal to moderate doses of a thiazide diuretic. In patients w ith severe volume depletion, use of AT(1) receptor antagonists may lead to acute renal failure. Valsartan was tested in a double-blind trial in patien ts with moderate to severe renal failure and led to a substantial decrease in diastolic and systolic blood pressure, whereas there was no difference f rom placebo for changes in GFR. Urine protein increased with placebo and de creased with valsartan. The data indicate that valsartan in renal failure p atients is effective in lowering blood pressure while leaving renal excreto ry function unaltered. Whether there is a renoprotective effect can only be shown in long-term trials, which are under way.