The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease

Abstract

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071–1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123–1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016–1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996–1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Late onset renal failure from angiotensin blockade (LORFFAB) and the syndrome of rapid onset endstage renal disease (SORO-ESRD) revisited – Two case reports from Mayo Clinic Health System, Northwestern Wisconsin, USA; a review paper

“…Quite often, the interval between the precipitating AKI event and the need for RRT is less than 2 weeks, and commonly is only in days following cardiothoracic procedures (7)(8)(9)(10). Following our reports on the syndrome of LORFFAB and having raised concerns regarding the unrecognized potential nephrotoxicity associated with angiotensin blockade, similar experiences have been observed in a few other centers around the world, including the work of El Nahas and his group from the Sheffield Kidney Institute, Sheffield, in the United Kingdom, implicating angiotensin blockade in the causation of clinically significant and sometimes unrecognized renal failure (11)(12)(13). In this article, we describe two representative case reports, one each of both syndromes, and discuss the implications of LORFFAB and SORO-ESRD in current nephrology practice paradigms.…”

“…It was indeed our work at the Mayo Clinic Health System in Northwestern Wisconsin that spurred the work of El Nahas and his group from the Sheffield Kidney Institute, Sheffield in the United Kingdom who concluded in 2010 that discontinuation of ACEI/ARB had undoubtedly delayed the onset of RRT in the majority of those studied and that this observation might justify a rethink of our approach to the inhibition of the renin-angiotensin-aldosterone system (RAAS) in patients with advanced CKD who are nearing the start of RRT (11,12). Some other investigators around the world have shown similar reports raising concerns about the potential nephrotoxicity of angiotensin blockade especially in the elderly (>65-year old) with more advanced CKD (13)(14)(15). As a result of these legitimate concerns, we now have a randomized controlled trial to determine whether the pre-emptive withdrawal of ACEI/ARB in patients with advanced CKD would result in improved cardiorenal outcomes -the ongoing STOP ACEi Trial (16,17).…”

Liraglutide Improves the Kidney Function in a Murine Model of Chronic Kidney Disease

“…The current CKD treatment options are limited to blood pressure control by blocking the renin angiotensin system (RAS), but these treatments do not reverse the CKD [4, 5]. Therefore, the search for improved CKD treatments is highly warranted.…”

Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria

“…In addition, combination treatments with ACEis and ARBs worsened the renal outcomes 45) . Moreover, a recent study by Oh et al 46) showed that habitual use of RAS blockade in predialysis patients with advanced CKD may have a detrimental effect on renal outcomes without improving all-cause mortality. We could not investigate how many patients had advanced CKD and how many patients had received combination treatment (ACEi and ARB), which is one of the limitations of the current study.…”