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

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 funct...

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Main Authors: Byorn W.L. Tan, Bryce W.Q. Tan, K. Akalya, Wei-Zhen Hong, Yi Da, Sanmay Low, Wan-Ying Ng, Horng-Ruey Chua
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Kidney Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590059525000329
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author Byorn W.L. Tan
Bryce W.Q. Tan
K. Akalya
Wei-Zhen Hong
Yi Da
Sanmay Low
Wan-Ying Ng
Horng-Ruey Chua
author_facet Byorn W.L. Tan
Bryce W.Q. Tan
K. Akalya
Wei-Zhen Hong
Yi Da
Sanmay Low
Wan-Ying Ng
Horng-Ruey Chua
author_sort Byorn W.L. Tan
collection DOAJ
description Rationale &amp; 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 &amp; 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; Pinteraction = 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; Pinteraction = 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. 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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spelling doaj-art-db3a923d59ae46ddad5f85e39fa49c6e2025-08-20T02:24:59ZengElsevierKidney Medicine2590-05952025-05-017510099610.1016/j.xkme.2025.100996Effect 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 StudyByorn W.L. Tan0Bryce W.Q. Tan1K. Akalya2Wei-Zhen Hong3Yi Da4Sanmay Low5Wan-Ying Ng6Horng-Ruey Chua7Department of Medicine, National University Hospital, SingaporeDepartment of Medicine, National University Hospital, SingaporeDivision of Nephrology, Department of Medicine, National University Hospital, SingaporeDivision of Nephrology, Department of Medicine, National University Hospital, Singapore; Fast and Chronic Programmes, Department of Medicine, Alexandra Hospital, SingaporeDivision of Nephrology, Department of Medicine, National University Hospital, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeDivision of Renal Medicine, Department of Medicine, Ng Teng Fong General Hospital, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Neurology, Department of Medicine, National University Hospital, SingaporeDivision of Nephrology, Department of Medicine, National University Hospital, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Address for Correspondence: Horng-Ruey Chua, MBBS, Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Level 10 Medicine Office, 1E Kent Ridge Road, National University Health System Tower Block, Singapore 119228.Rationale &amp; 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 &amp; 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; Pinteraction = 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; Pinteraction = 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. 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.http://www.sciencedirect.com/science/article/pii/S2590059525000329Acute kidney injuryangiotensin-converting enzyme inhibitorangiotensin receptor blockerchronic kidney diseasedialysismajor adverse kidney event
spellingShingle Byorn W.L. Tan
Bryce W.Q. Tan
K. Akalya
Wei-Zhen Hong
Yi Da
Sanmay Low
Wan-Ying Ng
Horng-Ruey Chua
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
Kidney Medicine
Acute kidney injury
angiotensin-converting enzyme inhibitor
angiotensin receptor blocker
chronic kidney disease
dialysis
major adverse kidney event
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Acute kidney injury
angiotensin-converting enzyme inhibitor
angiotensin receptor blocker
chronic kidney disease
dialysis
major adverse kidney event
url http://www.sciencedirect.com/science/article/pii/S2590059525000329
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