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Renin-Angiotensin-Aldosterone System Blockade after AKI with or without Recovery among US Veterans with Diabetic
Daniel P Murphy1, Julian Wolfson2, Scott Reule1,3
1Department of Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota.
Insights
In patients with acute kidney injury (AKI), using angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) was linked to reduced mortality. Earlier initiation of these medications after AKI showed greater benefits, irrespective of kidney function recovery.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- Optimal timing for angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) post-acute kidney injury (AKI) remains unclear.
- Concerns exist regarding potential delays in kidney function recovery or recurrent AKI with ACEi/ARB use.
- Conflicting data from prior studies highlight the need for clarity on ACEi/ARB use, especially considering kidney recovery status.
Purpose of the Study:
- To investigate the association between ACEi/ARB use after AKI and all-cause mortality in US Veterans with diabetes and proteinuria.
- To evaluate the impact of timing of ACEi/ARB initiation relative to AKI recovery on mortality outcomes.
Main Methods:
- Retrospective cohort study using electronic medical records of 54,735 US Veterans with AKI.
- ACEi/ARB treatment post-AKI defined as a time-varying exposure using Cox models.
- Kidney recovery defined as serum creatinine returning to ≤110% of baseline; mortality as the primary outcome.
Main Results:
- Post-AKI ACEi/ARB use was associated with a significantly lower risk of mortality (aHR, 0.74; 95% CI, 0.72 to 0.77).
- Earlier initiation of ACEi/ARBs after AKI demonstrated a stronger association with reduced mortality (P for interaction <0.001).
- Mortality risk was lower with ACEi/ARB use regardless of kidney recovery status, with benefits observed both before and after recovery.
Conclusions:
- ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI is associated with reduced mortality, irrespective of kidney recovery.
- Earlier initiation of ACEi/ARBs following AKI appears to be more beneficial.
- Findings support the use of ACEi/ARBs in this patient population, emphasizing timely initiation.
Significance Statement:
Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI.
Background:
Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain.
Methods:
Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after).
Results:
Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73).
Conclusions:
This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation.
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