Clinical Question: Does discontinuation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during an episode of acute kidney injury (AKI) improve clinical outcomes in hospitalized patients?
Background: AKI is an extremely common condition in hospitalized patients and is associated with increased risk of mortality. Despite the widespread use of ACEIs and ARBs, there are no published studies that evaluate the survival effect of continuing these medications during AKI in hospitalized patients.
Study Design: Multi-database cohort study using sequential target-trial emulation
Setting: Twenty-eight regional medical centers in China (included in the CRDS database), and at Beth Israel Deaconess Medical Center in Boston (included in the MIMIC-IV database)
Synopsis: Adult patients with hospital-acquired AKI and ACEI or ARB use at least 90 days prior were included, and discontinuation within two days of AKI was used for group stratification. The primary outcome was 30- and 180-day all-cause mortality, and the secondary outcome was AKI recovery.
In the 21,680-person trials from CRDS, the risk difference in 30-day and 180-day all-cause mortality was -1.55% (CI, -2.43% to -0.55%), and -3.12% (CI, -4.94% to -1.03%) for those who discontinued ACEIs or ARBs compared to those who continued them, respectively. In the 5,323-person trials from MIMIC-IV, the risk difference in 30-day and 180-day all-cause mortality for patients who discontinued was -0.79% (CI, -1.61% to -0.12%) and -1.98% (CI, -3.80% to -0.28%), respectively. These findings were consistent across subgroups, and the beneficial association of discontinuation was greatest among patients at highest mortality risk. For AKI recovery, the risk difference for those who discontinued was 8.92% (CI, 5.17% to 13.13%) in CRDS and 6.51% (CI, 3.02% to 9.60%) in MIMIC-IV. The benefits of discontinuation were consistent across sensitivity analyses.
Bottom Line: Discontinuation of ACEIs or ARBs within the first two days of an episode of AKI in hospitalized patients was associated with decreased all-cause mortality.
Citation: Nie S, et al. Discontinuation of renin-angiotensin system inhibitors during acute kidney injury episode and all-cause mortality: target trial emulation studies. J Am Soc Nephrol. 2025;36(12):2410-2420. doi:10.1681/ASN.0000000775.
Dr. Bonifacino
Dr. Bonifacino is an academic hospitalist in the division of hospital medicine at MedStar Washington Hospital Center and an associate professor of medicine at Georgetown University School of Medicine, both in Washington, D.C.