The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease

We read with fascination and an intense feeling of déjà vu the recent brilliant report by El Nahas et al. on the impact of stopping renin-angiotensin system (RAAS) blockade in patients with advanced chronic kidney disease (CKD) [1]. The authors demonstrated clinically significant and sustained increases in estimated glomerular filtration rate (eGFR) following drug discontinuation without any changes in proteinuria [1]. eGFR increased from 16.38 to 26.6 ml/min/1.73 m2, and these increases in eGFR were sustained beyond 24 months [1]. Of note, the 52-patient cohort had a mean age of 73 years. Since 2005, and more so in 2008 and 2009, we have published several reports on the previously unknown syndrome of late-onset renal failure from angiotensin blockade (LORFFAB) [2,3]. We submit that the report by El Nahas et al. is a vindication and substantiation of our hypothesis for this formerly unrecognized syndrome of iatrogenic renal failure occurring especially in older (>65 years old) CKD patients concurrently on RAAS blockade and that discontinuation of RAAS blockade often leads to clinically significant and sustained improvements in eGFR [2–4]. Presently, in the USA, despite the very widespread and escalating application of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for touted renoprotection, we continue to experience an ever-increasing end-stage renal disease (ESRD) epidemic [2–4]. There is increasing evidence of iatrogenic renal failure from the use of these agents in older CKD patients, including reversible acute renal failure following drug discontinuation and sometimes irreversible ESRD [1–4]. The exact contribution of LORFFAB, as we had described it [2,3] and as El Nahas et al. have demonstrated in their report [1], to the ESRD epidemic, for now, can only remain conjectural [1–5]. Larger randomized placebo-controlled trials (RCT) to investigate this phenomenon to the fullest are warranted. Furthermore, we have observed that the large RCT RAAS blockade studies like Candesartan in Heart failure-Assessment of Reduction in Mortality and Morbidity (CHARM) and Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) had failed to highlight a significant increase in renal failure incidence, including ESRD, among patients who received ACEIs or ARBs [2,3,5]. For instance, in the ALLHAT study, diabetics in the lisinopril (ACEI) group experienced a higher ESRD rate compared to the chlorthalidone (diuretic) group [5]. In our opinion, there appears to be reluctance on the part of the ‘establishment’ to more forcefully report on adverse renal outcomes associated with the use of ACEIs and ARBs in these RCT reports [5]. Finally, we would like to congratulate El Nahas et al. and the editor of Nephrology, Dialysis and Transplantation for the academic courage to publish this report. Editorial Note: Prof. El Nahas et al. had no further comments on this letter and thank the authors for their insight and appreciation. Conflict of interest statement. None declared.