Benefits and risks of dual inhibition of the renin– angiotensin aldosterone system for kidney disease

A In most cases, neither angiotensin converting enzyme (ACE) inhibitor therapy nor angiotensin II receptor blockers (ARBs) therapy alone inhibits completely the renin-angiotensin aldosterone system (RAAS). The drawbacks of ACE inhibitors are the ACE escape and aldosterone escape phenomenon, which are related to the tissue construction of angiotensin II and aldosterone by enzymes besides ACE. Combination of RAAS inhibition may avoid the ACE and aldosterone escape events that increases the efficiency of ACE inhibitors and ARBs and obstruct all angiotensin II and aldosterone actions accordingly. ONTARGET, largest trial of combination against alone RAAS blockade therapy in patients with vascular diseases or diabetes along with disease of such organs displayed that combination therapy advised no extra-benefit in reducing advance to end-stage renal disease in diabetic patients and decreasing the risk of cardiovascular. Certainly, in this trial, the administration of dual RAAS blockade therapy of an ACE inhibitor plus ARB was correlated with a higher degree of side effects in comparison to monotherapy. In addition to the study of ONTARGET, the ORIENT, VALIANT, VA NEPHRON-D and HALT-PKD trials also proved this finding. Adverse events associated with combination therapy of ACE inhibitor plus ARB is including hyperkalemia, low blood pressure, acute kidney injury (AKI) and withdrawal because of side effects.