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

Yun Jung Oh,Jae Hyun Chang,Wookyung Chung,Byung Chul Shin,Jong Hoon Chung,Ae Jin Kim,Chungsik Lee,Hyun Lee Kim,Hyun Hee Lee,Sun Moon Kim,Ji Yong Jung,Han Ro,Tatsuo Shimosawa

doi:10.1371/journal.pone.0170874

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.

Highlights

The use of renin-angiotensin system (RAS) blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are first-line options for reducing proteinuria and slowing the progression of nephropathy in diabetic patients
The adjusted hazard ratios (HRs) for end-stage renal disease (ESRD) (HR, 1.383; 95% confidence intervals (CIs), 1.107–1.729; P = 0.004) was significantly higher in ACEI/ARB users compared to non-users, but the adjusted HR for the composite outcome was not different between the two groups (HR, 1.180; 95% CI, 0.980–1.420; P = 0.080; Table 2)
In this study, which was conducted in pre-dialysis patients with advanced chronic kidney disease (CKD), the use of ACEI/ARB was associated with an increased risk of developing ESRD, necessitating long-term dialysis and the composite outcome of ESRD or death from any cause, or hospitalization for hyperkalemia

Summary

Introduction

The use of renin-angiotensin system (RAS) blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are first-line options for reducing proteinuria and slowing the progression of nephropathy in diabetic patients. Other previous studies have reported positive results for RAS blockades, they were not superior to other drugs in terms of reducing renal progression or the long-term risk of ESRD [23,24,25]. These findings raise a question about the advantage of ACEI/ARB in terms of renoprotection

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Results

Conclusion