Analytical Review of the Evidence for Renoprotection by Renin-Angiotensin-Aldosterone System Blockade in Chronic Kidney Disease – A Call for Caution

Despite reported renoprotection with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and notwithstanding their increased use, we continue to experience an epidemic of acute renal failure (ARF)/chronic kidney disease/end-stage renal disease. Consequently, concerns about iatrogenic renal failure have resurfaced. Different analysis of these trials revealed flaws such as recruitment of relatively younger patients with preserved baseline renal function, common utilization of lower end doses of ACEIs/ARBs, high drug discontinuation rates, excessive use of surrogate endpoints, inadequate reporting of adverse effects, and short duration studies. Again, lower 24-hour ambulatory blood pressure among patients in the ramipril arm of the micro-HOPE (Heart Outcomes Prevention Evaluation) study raises doubts of renoprotection beyond blood pressure lowering. The disappointing results from the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study only compounded these doubts. We demonstrated significant renal salvage after ACEI/ARB was discontinued in chronic kidney disease patients recruited with increasing ARF while on ACEI/ARB. Apart from our reports, there are increasing reports incriminating the use of ACEI/ARB with ARF exacerbations. We conclude that close and indefinite monitoring of estimated glomerular filtration rate is an absolute must in these patients. The treating physician must be ready to consider trial discontinuation of ACEI/ARB, promptly. Combination ACEI + ARB therapy should be the exception, rather than the rule. Temporary withdrawal of ACEI/ARB before certain exposures, ‘renoprevention’, would only further improve the results of renoprotection.