COMMENTARY

ARBs/ACEIs After Acute Kidney Injury: Balancing Tradeoffs

Nisha Bansal, MD, MAS

Disclosures

December 20, 2018

Acute kidney injury (AKI) is common in hospitalized patients and rates continue to rise. After an episode of AKI, numerous studies have shown a link with poor clinical outcomes, including greater risk for progression to end-stage renal disease (ESRD), death, and cardiovascular disease.[1,2,3,4] Despite the high risk for poor outcomes, post-AKI management remains elusive.

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) are frequently discontinued during AKI episodes. When and whether to restart ACEI/ARBs after an AKI remains unknown, despite evidence that demonstrates that renin-angiotensin-aldosterone system (RAAS) inhibition is effective in reducing kidney and cardiovascular events as well as mortality.

In a recent issue of JAMA Internal Medicine, Brar and colleagues evaluated whether the use of ACEI or ARBs after hospital discharge was associated with better outcomes in patients with AKI.[5] To conduct this study, the authors performed a retrospective analysis using data from the Alberta (Canada) Kidney Disease Network population. Patients who experienced a hospitalization with AKI (defined as 50% increase between prehospital and peak in-hospital serum creatinine) and survived to hospital discharge were included in the analysis. Propensity scores were used to match pairs of patients who experienced a hospitalization for AKI who did versus did not receive a prescription for an ACEI or ARB within 6 months after hospital discharge. The primary outcome was mortality. Secondary outcomes included kidney-related hospitalizations, ESRD, or a composite outcome of ESRD or doubling of serum creatinine.

Of the 46,253 patients included in the analysis, 48% of participants were prescribed an ACEI or ARB within 6 months after hospital discharge. When approximately 9400 ACEI/ARB users were matched with nonusers and adjusted for numerous patient characteristics, a 15% lower risk for all-cause mortality was observed for ACEI/ARB users. However, greater risks for adverse kidney events were observed in the ACEI/ARB users (28% higher risk for a hospitalization related to a kidney cause and 25% higher risk for AKI). Furthermore, a greater risk for heart failure was noted with a 69% greater risk in the ACEI/ARB users compared with nonusers. There was no difference between the groups for the outcomes of hypervolemia, hyperkalemia, hypertension, or ESRD.

Both new ACEI/ARB use (15% reduction) and continued ACEI/ARB use (23% reduction) after hospital discharge were associated with lower mortality compared with no ACEI/ARB use. In contrast, stopping use of an ACEI/ARB prescribed before hospital admission was associated with 23% increased risk for mortality.

When examining subgroups for presence of proteinuria, baseline estimated glomerular filtration rate (eGFR), diabetes, hypertension, heart failure, and myocardial infarction/stroke, the association of use of ACEI/ARB with mortality was fairly similar. However, there was a stronger association of ACEI/ARB use among patients with eGFR ≥ 60 mL/min/1.73 m2 (19% reduction in mortality risk vs 11% as seen in those with eGFR < 60 mL/min/1.73 m2) as well as those with hypertension (16% reduction in mortality risk vs no association in patients without hypertension).

Where Does This Study Leave Us?

The strengths of this study include large, population-based sample and information on many possible confounders. However, the study was observational, and so even with propensity score matching, issues of confounding by indication remain and may explain the paradoxical association seen with ACEI/ARB use and risk for heart failure in this study.

Furthermore, while the authors were able to quantify RAAS inhibitor use through prescriptions, data on adherence were not available. Data on the etiology of AKI as well as the resolution of AKI were not presented, which may affect post-AKI outcomes and management.

Even with these limitations, this study provides important data on the use of RAAS inhibitors after AKI, an area of clinical importance that remains understudied. Kidney Disease Improving Global Outcomes (KDIGO) AKI guidelines recommend that patients be followed for 3 months after an episode of AKI.[6] Yet, there remains little guidance on what care should be provided during those 3 months.

The data from this study may help guide implementation of RAAS inhibitors, which are widely available, in this high-risk population. However, further studies, preferably interventional, are needed to better understand the risks versus benefits as well as the optimal timing of RAAS inhibitors after an episode of AKI. Improving post-AKI care should be a priority to mitigate short- and long-term adverse clinical outcomes.

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