Time-varying metoprolol exposure and the risk of acute kidney injury: a multicenter retrospective cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Evidence regarding the association between metoprolol use and acute kidney injury (AKI) remains limited, particularly because of time-varying exposure, cardiovascular confounding, and uncertain temporal ordering. We evaluated the association between recent metoprolol exposure and incident AKI using a longitudinal time-varying framework. Methods This multicenter retrospective longitudinal cohort study included adult inpatients from three Chinese hospitals between January 2020 and December 2024. Eligible patients had an estimated glomerular filtration rate ≥60 mL min -1 ·1.73 m -2 at cohort entry and sufficient serial serum creatinine (Scr) and medication execution records. Metoprolol was modeled as a lag-1 time-varying exposure, relating use on hospital day t to AKI risk on day t +1. Incident AKI was identified using rolling KDIGO Scr criteria. Time-varying Cox regression adjusted for demographic characteristics, baseline renal function, major comorbidities, baseline severity-related factors, and lagged concomitant medication exposures. Sensitivity and complementary analyses evaluated the robustness of the findings. Results Among 291,049 screened hospitalizations, 20,333 patients contributed 284,470 risk intervals, and 1,050 developed incident AKI. Lag-1 metoprolol exposure was associated with a higher AKI hazard in the unadjusted model (HR, 2.53; 95% CI, 2.13–3.00). The association was substantially attenuated after adjustment but remained statistically significant in the primary model (HR, 1.37; 95% CI, 1.05–1.79; P = 0.022). Prespecified follow-up-time analyses suggested that the association was concentrated during the first 72 h after cohort entry. Sensitivity analyses generally yielded estimates in the same direction, although the magnitude and statistical significance varied across analytical specifications; the association was attenuated to non-significance in the 2-day lag analysis (HR, 1.27; 95% CI, 0.96–1.68) and after additional adjustment for vasopressor use (HR, 1.29; 95% CI, 0.98–1.70). No consistent monotonic dose–response relationship was observed. Conclusion Recent metoprolol exposure was associated with a modestly higher hazard of incident AKI in the primary adjusted analysis. However, attenuation after adjustment, temporal heterogeneity, sensitivity to exposure timing and confounding control, and the absence of a consistent monotonic dose–response pattern suggest that residual confounding and clinical treatment context may contribute to the observed association. These findings should be interpreted as a hypothesis-generating short-term AKI safety signal rather than evidence of direct metoprolol nephrotoxicity or causality.
Source: Frontiers in Pharmacology
Institution: Chinese People's Liberation Army
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223178090