Association of serum urate trajectories and visit-to-visit variability with rapid egfr decline: a 5-year community cohort study

Background Whether serum urate (SUA) is independently associated with kidney function decline, and the threshold at which risk rises, remain unclear. Most prior studies used single measurements, ignoring long-term patterns or variability. Methods We followed 628 Chinese adults with five annual health examinations (2021–2025). Each year we measured SUA and eGFR (2021 CKD-EPI creatinine equation). Rapid eGFR decline was defined as an annual slope steeper than − 5 mL/min/1.73 m². Restricted cubic splines assessed the dose-response relationship. Latent-class growth modeling identified 5-year SUA trajectories. Visit-to-visit SUA variability was calculated adjusting for mean urate levels. A descriptive path analysis quantified the fraction of the association statistically explained by systolic blood pressure (SBP) changes. Results Mean eGFR fell from 94.8 to 89.3 over five annual visits; 15.6% had rapid decline. The dose-response was non-linear ( p = 0.024), with risk rising notably at higher SUA concentrations. The lower end of the curve had wide confidence intervals including the null, so a definitive J-shaped relationship cannot be claimed. Four trajectories emerged: Low-Stable (34.6%), Moderate-Stable (31.8%), High-Stable (22.3%), and Rapid-Increasing (11.3%). Versus Low-Stable, adjusted odds ratios for rapid decline were 2.54 (95% CI 1.72–3.74) for High-Stable and 2.00 (1.28–3.13) for Rapid-Increasing. Higher SUA variability was independently associated with rapid decline (highest vs. lowest SD tertile: OR = 1.95, 95% CI 1.28–2.97). SBP change statistically explained 20.7% of the total association; this does not imply a direct causal effect. Among 138 participants with baseline hyperuricemia, those who achieved normouricemia by 2025 had smaller 5-year eGFR decline (− 3.9 vs. −7.8; adjusted difference + 3.5, 95% CI 1.8–5.2). However, this was a post-hoc non-randomized comparison and is hypothesis-generating only. Conclusions Both SUA level and its long-term longitudinal patterns were independently associated with rapid eGFR decline in this community cohort. The association was only partly explained by change in systolic blood pressure, but this does not establish that the urate–kidney association is independent of blood pressure. Whether repeated SUA measurements add incremental value for risk stratification requires prospective evaluation. Whether lowering or stabilising urate can modify this risk remains unknown and requires randomized trials. These findings are observational and cannot establish causality.