Comparison of dual RAAS blockade and higher-dose RAAS inhibition on nephropathy progression

Although the risk of dying from cardiovascular disease (CVD) is greater than for progressing to end-stage renal disease (ESRD), the increasing prevalence of diabetes mellitus and reduced mortality from CVD have contributed to an increased incidence of ESRD. Use of renin-angiotensin-aldosterone system (RAAS) blockers to reduce blood pressure is proven to reduce the rate of nephropathy progression. Theoretically, more complete RAAS inhibition may enhance the ability to slow nephropathy progression. Combining an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) more completely inhibits the RAAS, potentially providing greater opportunity for renoprotection. Proteinuria is a strong independent predictor of poor renal and cardiovascular outcomes. Therefore, targeting interventions that further reduce proteinuria may yield better outcomes. This review presents evidence supporting the hypothesis that higher doses of RAAS inhibition or dual RAAS blockade are more effective in reducing proteinuria. Clinical data and ongoing trials will be discussed in the context of this hypothesis.