Recent metoprolol use linked to modestly elevated acute kidney injury risk

A multicenter retrospective cohort study found that recent exposure to metoprolol was associated with a modestly higher hazard of acute kidney injury among hospitalized adults, but the results do not establish that metoprolol directly damages the kidneys or caused the outcomes. The analysis included 20,333 patients treated at three Chinese hospitals between January 2020 and December 2024. Of these patients, 1,050 developed incident acute kidney injury, or AKI.

To account for medication exposure and kidney function that could change during hospitalization, investigators modeled metoprolol use as a time-varying exposure. Use on a hospital day was related to the risk of AKI on the following day. Eligible patients had an estimated glomerular filtration rate of at least 60 mL/min/1.73 m² at cohort entry and sufficient serial serum creatinine and medication-execution records. The study generated 284,470 risk intervals for the 20,333 participants, with incident AKI identified using rolling KDIGO serum-creatinine criteria.

In the unadjusted time-varying Cox model, lag-one metoprolol exposure was associated with a substantially higher AKI hazard, with a hazard ratio of 2.53 and a 95% confidence interval of 2.13 to 3.00. The association was substantially attenuated after adjustment for demographic characteristics, baseline renal function, major comorbidities, baseline severity-related factors and lagged concomitant medication exposures. It nevertheless remained statistically significant in the primary adjusted model: the hazard ratio was 1.37, the 95% confidence interval was 1.05 to 1.79, and P = 0.022. The change after adjustment indicates that measured differences in patient characteristics, clinical condition and concurrent treatments accounted for part of the unadjusted association, although the analysis could not eliminate residual confounding.

The pattern varied across follow-up-time and sensitivity analyses. Prespecified analyses suggested that the association was concentrated during the first 72 hours after cohort entry rather than remaining constant throughout follow-up. Most analytical specifications produced estimates in the same direction, but their magnitude and statistical significance varied. The association was attenuated to non-significance in the two-day lag analysis, with a hazard ratio of 1.27 and a 95% confidence interval of 0.96 to 1.68, and after additional adjustment for vasopressor use, with a hazard ratio of 1.29 and a 95% confidence interval of 0.98 to 1.70. No consistent monotonic dose-response relationship was observed. These findings leave uncertainty about the role of exposure timing and the clinical circumstances in which metoprolol was prescribed.

Because the study was retrospective and observational, the results cannot determine whether metoprolol contributed to AKI or whether residual differences between treatment groups explain the adjusted association. The concentration of the signal during early follow-up, its sensitivity to the lag definition and further confounding control, and the absence of a consistent dose-response pattern limit causal interpretation. The evidence therefore supports interpreting the results as a hypothesis-generating short-term AKI safety signal rather than evidence of direct metoprolol nephrotoxicity or causality.

Subject of Research: Association of recent metoprolol exposure with incident acute kidney injury in hospitalized adults

Article Title: Time-varying metoprolol exposure and the risk of acute kidney injury: a multicenter retrospective cohort study

Article References: Li, Z., Zha, H., Gong, Q., Wu, M., She, Y., & Xu, F. (2026). Time-varying metoprolol exposure and the risk of acute kidney injury: a multicenter retrospective cohort study. Frontiers in Pharmacology, 17, Article 1899992. https://doi.org/10.3389/fphar.2026.1899992

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DOI: 10.3389/fphar.2026.1899992

Keywords: metoprolol, acute kidney injury, time-varying exposure, hospitalized adults, retrospective cohort, serum creatinine, renal function, residual confounding, medication safety, Time-varying, exposure, risk