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

Date Published: January 25, 2017

Publisher: Public Library of Science

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


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.

Partial Text

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. Moreover, RAS blockers are the antihypertensive drugs of choice in patients with non-diabetic chronic kidney disease (CKD) [1–4]. These recommendations are based on numerous reports that RAS blockers are more effective in slowing renal progression than other antihypertensive agents [5–11]. However, despite the use of RAS blockers to prevent the progression of CKD in the last two decades, the incidence of end-stage renal disease (ESRD) has continued to increase [12–15].

In this study, which was conducted in pre-dialysis patients with advanced CKD (stages 4 and 5), 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. After controlling for potential confounding factors using PS matching and IPTW, the findings suggested an increased risk of ESRD, but no difference in all-cause mortality, in ACEI/ARB users compared to non-users. This suggests that the use of RAS blockers in this patient population may accelerate progression to ESRD without enhancing survival.




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