Renin-angiotensin-aldosterone system blockade for nephroprotection: current evidence and future directions

Renin-angiotensin-aldosterone system (RAAS) blockade is currently the best-documented treatment strategy to delay the progression of chronic proteinuric nephropathies. Several large randomized controlled trials have shown the renoprotective potential of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and the direct renin inhibitor aliskiren as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and retard development of renal dysfunction more than placebo. No clinical evidence is available, however, about whether these strategies may influence long-term kidney disease outcomes. Combined RAAS blockade may be offered only to patients with proteinuric chronic nephropathies who do not achieve full and persistent remission of proteinuria with ACEI or ARB alone. They need to be carefully monitored for hyperkalemia and worsening of kidney function. This article reviews an evidence-based approach to use of RAAS-inhibiting agents in kidney diseases, considers combination RAAS blockade treatment strategies and discusses some perspectives related to the implementation of RAAS blockade in renal protection.