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. 2025 Mar 20;7(5):100996.
doi: 10.1016/j.xkme.2025.100996. eCollection 2025 May.

Effect of Post-Acute Kidney Injury Use of Renin-Angiotensin Inhibitors on Long-term Mortality and Major Adverse Kidney Events: A 5-year Retrospective Observational Cohort Study

Byorn W L Tan  1 , Bryce W Q Tan  1 , K Akalya  2 , Wei-Zhen Hong  2   3 , Yi Da  2   4 , Sanmay Low  5 , Wan-Ying Ng  4   6 , Horng-Ruey Chua  2   4
Affiliations

Effect of Post-Acute Kidney Injury Use of Renin-Angiotensin Inhibitors on Long-term Mortality and Major Adverse Kidney Events: A 5-year Retrospective Observational Cohort Study

Byorn W L Tan et al. Kidney Med. .

Abstract

Rationale & objective: Acute kidney injury (AKI) is common in hospitalized adults and a risk factor for chronic kidney disease and mortality. The effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) post-AKI on mortality and long-term kidney function remains unclear.

Study design: Propensity-weighted retrospective observational cohort study.

Setting & participants: A total of 3,289 patients with AKI admitted to a tertiary care hospital from November 2015-October 2016, with follow-up until September 2020.

Exposures: ACEi/ARB use within 180 days post-AKI.

Outcomes: All-cause mortality, and major adverse kidney events (MAKE) as defined by composite of renal replacement therapy post-AKI, sustained estimated glomerular filtration rate (eGFR) decline >30% from baseline, or eGFR ≤15 mL/min/1.73 m2.

Analytical approach: We generated propensity weights for ACEi/ARB use post-AKI, using age, sex, comorbid conditions, prior medication, intensive care unit admission, severe sepsis, and index AKI Kidney Disease: Improving Global Outcomes severity. Cox proportional hazard models were used to test associations of post-AKI ACEi/ARB with mortality, MAKE, and joint models for eGFR slopes.

Results: A total of 2,309 (70.2%) participants died or experienced MAKE by end of follow-up. 161 (4.9%) and 406 (12.3%) patients initiated or resumed prior ACEi/ARB use within 180 days post-AKI, respectively. Although the overall cohort had no significant mortality association with post-AKI ACEi/ARB use, a significant association with lower mortality was observed in patients with KDIGO 3 AKI (HR, 0.40; 95% CI, 0.21-0.75; P interaction = 0.003). However, post-AKI ACEi/ARB use was associated with increased MAKE in patients without cardiovascular indications for ACEi/ARB use (HR, 1.52; 95% CI, 1.17-1.98; P interaction = 0.03). Although post-AKI use of ACEi/ARB was associated with acute eGFR decline (initial eGFR change -2.3 mL/min/1.73 m2/year; 95% CI, -3.1 to -1.5; P < 0.001), no association with longer-term eGFR decline was observed.

Limitations: Retrospective observational study on heterogeneous AKI cohort without data on ACEi/ARB cumulative exposure.

Conclusions: Early ACEi/ARB post-AKI was not associated with better long-term survival or kidney function but was associated with lower mortality in patients with KDIGO 3 AKI.

Keywords: Acute kidney injury; angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; chronic kidney disease; dialysis; major adverse kidney event; mortality; renal replacement therapy.

Plain language summary

Acute kidney injury (AKI) is common in hospitalized adults and increases the risk of death and kidney failure. Although angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) have been widely used in proteinuric kidney disease to slow kidney function decline, the effect of ACEi/ARB use post-AKI on long-term kidney function remains unclear. In this 5-year study of 3,289 patients with AKI, we found that although patients experienced a transient decrease in kidney function following early ACEi/ARB initiation after their kidney injury, long-term kidney function trajectory and survival in these patients were similar to patients without early ACEi/ARB use. However, ACEi/ARB use after an AKI may reduce the long-term risk of death in patients with severe AKI. Additionally, we noted sustained kidney function deterioration in a subgroup of patients on ACEi/ARB early post-AKI in the absence of cardiovascular indications. These observations suggest that clinicians should adopt more individualized approaches to early ACEi/ARB administration post-AKI.

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Figures

Figure 1
Figure 1
Flowchart of inclusion and exclusion criteria for the patient cohort used in the current study. Abbreviations: AKI, acute kidney injury; eGFR, estimated glomerular filtration rate; RRT, renal replacement therapy; sCr, serum creatinine.
Figure 2
Figure 2
MAKE and mortality in patients with and without post-AKI use of ACEi/ARB. (A) Cumulative incidence curve of MAKE, with mortality as a competing event, in the overall cohort, stratified by the presence or absence of post-AKI use of ACEi/ARB. Curves were weighted with inverse propensity of treatment weighting and covariate balancing. P values were determined using Pepe and Fleming’s test. Shaded areas represent 95% CIs. Tick marks represent time of censoring. Dashed lines in survival curves represent median or 75th percentiles as specified, colored dashed lines in cumulative incidence curves for MAKE represent death as a competing event, and black dashed lines in cumulative incidence curves represent MAKE cumulative incidence at 1,080 days. (B) Survival curve representing the composite event of MAKE and mortality, stratified by the presence or absence of post-AKI use of ACEi/ARB. Curves were weighted with inverse propensity of treatment weighting and covariate balancing. P values were determined using Pepe and Fleming’s test. Shaded areas represent 95% CIs. Tick marks represent time of censoring. Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; AKI, acute kidney injury; CI, confidence interval; MAKE, major adverse kidney event; sCr, serum creatinine.
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