Front Nutr. 2026 Sep 16;13:1919779. doi: 10.3389/fnut.2026.1919779. eCollection 2026.
ABSTRACT
INRODUCTION: Within-person variation in serum uric acid (SUA) may reflect clinical instability, but its association with outcomes in chronic kidney disease (CKD) is uncertain.
METHODS: We studied 10,556 adults with EHR-defined CKD and at least three SUA measurements during a 365-day baseline window across a nine-hospital consortium. Variability was quantified primarily by the coefficient of variation (CV); the primary outcome was all-cause mortality, and secondary outcomes were a composite kidney endpoint and major adverse cardiovascular events (MACE). Cox models adjusted for demographics, comorbidities, baseline laboratory values, mean SUA, measurement number and medication use. Reproducibility of the short-term mortality association was assessed in MIMIC-IV.
RESULTS: During a median follow-up of 0.62 years, 649 deaths, 676 kidney events and 3,172 first MACE occurred. Higher SUA CV was associated with mortality in the fully adjusted model (hazard ratio [HR] per 1-SD increase 1.24, 95% CI 1.15-1.32; highest versus lowest tertile 1.87, 95% CI 1.50-2.33), whereas adjusted associations with kidney events (HR 1.01, 95% CI 0.93-1.10) and MACE (HR 1.02, 95% CI 0.98-1.05) were null. Of all deaths, 495 (76.3%) occurred within 90 days. In a post-90-day landmark analysis of 6,784 participants with more than 90 days of follow-up, the mortality association was not observed (154 deaths; HR 1.02, 95% CI 0.86-1.21). Results were similar after daily aggregation of SUA measurements and additional adjustment for urate-lowering therapy, colchicine and sodium-glucose cotransporter-2 inhibitors. In MIMIC-IV (n = 5,350; 931 deaths within 90 days), the adjusted HR per 1-SD increase in CV was 1.32 (95% CI 1.26-1.38).
DISCUSSION: Greater SUA variability was associated with mortality during short follow-up; the concentration of deaths within 90 days and the null post-90-day landmark estimate suggest that the exposure may primarily mark near-term clinical deterioration rather than a causal or durable long-term prognostic mechanism.
PMID:42818760 | PMC:PMC13623910 | DOI:10.3389/fnut.2026.1919779