Impact of Different Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blocker Resumption Timing on Post Acute Kidney Injury Outcomes

Abstract

Introduction: Evidence suggests a survival benefit from resuming angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) post acute kidney injury (AKI) compared to nonuse; however, the optimal timing and its impact on outcomes are unclear. The risks of earlier resumption, such as recurrent AKI or hyperkalemia, remain unexplored.

Methods: Using multiinstitutional electronic health records, we analyzed the relationship between 3 ACEI or ARB (ACEI/ARB) resumption timelines post-AKI (prior to discharge, 0-3 months, and 4-6 months postdischarge) and outcomes including all-cause mortality, major adverse cardiac and cerebrovascular events (MACCEs), dialysis initiation or end-stage renal disease (ESRD), severe hyperkalemia, and recurrent AKI with hospitalization. Cox proportional models estimated hazard ratios (HRs) for outcomes across different resumption timings, following a target trial design.

Results: Among 5392 AKI survivors resuming ACEI/ARB within 6 months post-AKI, earlier resumption was associated with lower mortality, MACCE, MACCE-related mortality, new dialysis initiation or ESRD (P < 0.001 in trend tests), without increased risks of severe hyperkalemia and re-AKI admissions. Early resumption has a lower mortality compared to 4 to 6 months postdischarge (before discharge, HR: 0.88, 95% confidence interval [CI]: 0.83-0.93; 0-3 months, HR: 0.89, 95% CI: 0.85-0.94). Subgroup analysis showed a lower mortality HR from earlier resumption among AKI survivors with prior ACEI/ARB comorbidity indications (P < 0.001 in trend tests; before discharge, HR: 0.85, 95% CI: 0.80-0.90; 0-3 months, HR: 0.88, 95% CI: 0.83-0.93).

Conclusion: Our cohort demonstrates lower risks for mortality, cardiovascular events, and ESRD with early ACEI/ARB resumption, without heightened risks of severe hyperkalemia or rehospitalization for AKI. Early resumption should be considered for patients with indications for ACEI/ARB.

Keywords: ACEI; ARB; RAAs inhibitor; acute kidney disease; acute kidney injury; resumption.

Graphical abstract

Figure 1

Flow diagram for the inclusion and exclusion of study patients. ACEI, angiotensin converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ESRD, end-stage renal disease.

Figure 2

Cumulative event rates by timing of ACEI/ARB resumption: (a) MACCE, (b) new dialysis/ESRD, (c) cardiovascular death, (d) all-cause mortality, (e) severe hyperkalemia, (f) recurrent AKI admission. ACEI, angiotensin- converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; ESRD, end-stage renal disease; IPTW, inverse probability of treatment weighting; MACCE, major adverse cardiac and cerebrovascular events.

Figure 3

eGFR decline and slope after ACEI/ARB resumption in the IPTW-adjusted cohort. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate; IPTW, inverse probability of treatment weighting. The slope of eGFR decline during 3-year follow-up after discharge day from the index AKI admission in each study group were estimated using the linear mixed model which treated participants as random effect.