Five-Year Serum Urate Patterns Tied to Faster Kidney Function Decline

Adults whose serum urate levels stayed high over five years, or whose levels varied widely from visit to visit, were more likely to experience rapid decline in kidney function, according to a community cohort study of 628 Chinese adults published in BMC Nephrology. The study followed participants through five annual health examinations between 2021 and 2025, measuring serum urate and estimated glomerular filtration rate, or eGFR, at each visit using the 2021 CKD-EPI creatinine equation.

Rapid eGFR decline was defined as an annual slope steeper than −5 mL/min/1.73 m². Over the five annual visits, mean eGFR in the cohort fell from 94.8 to 89.3, and 15.6% of participants met the definition of rapid decline. Because the design is observational, the findings show association rather than causation, a limitation the authors state explicitly.

The researchers used restricted cubic splines to examine the dose-response relationship between urate concentration and kidney decline. The relationship was non-linear (p = 0.024), with risk rising notably at higher serum urate concentrations. However, the lower end of the curve had wide confidence intervals that included the null value, meaning a definitive J-shaped relationship cannot be claimed from these data.

To capture long-term urate patterns rather than single snapshots, the team applied latent-class growth modeling to the five annual measurements. Four distinct trajectories emerged: a Low-Stable group comprising 34.6% of participants, a Moderate-Stable group at 31.8%, a High-Stable group at 22.3%, and a Rapid-Increasing group at 11.3%. Compared with the Low-Stable group, the adjusted odds ratio for rapid eGFR decline was 2.54 (95% CI 1.72–3.74) for the High-Stable group and 2.00 (95% CI 1.28–3.13) for the Rapid-Increasing group.

Variability also mattered. The researchers calculated visit-to-visit serum urate variability with adjustment for mean urate levels, and found that higher variability was independently associated with rapid decline. Participants in the highest tertile of variability had an odds ratio of 1.95 (95% CI 1.28–2.97) compared with those in the lowest tertile.

The study also explored whether blood pressure changes might account for part of the association. A descriptive path analysis estimated that change in systolic blood pressure statistically explained 20.7% of the total association between urate patterns and rapid eGFR decline. The authors caution that this statistical fraction does not imply a direct causal effect, and that the result does not establish that the urate–kidney association is independent of blood pressure.

A post-hoc comparison within the cohort added a hypothesis-generating observation. Among 138 participants who had hyperuricemia at baseline, those who achieved normouricemia by 2025 showed a smaller five-year eGFR decline than those who did not: −3.9 versus −7.8, an adjusted difference of +3.5 (95% CI 1.8–5.2). Because this comparison was non-randomized and conducted after the fact, the authors describe it as hypothesis-generating only, not evidence that lowering urate protects the kidneys.

The motivation for the study reflects a gap in earlier research. Whether serum urate is independently associated with kidney function decline, and at what threshold risk rises, has remained unclear, and most prior studies relied on single measurements that ignored long-term patterns and variability. By tracking repeated measurements over five years, this cohort offers a more detailed longitudinal picture, though it cannot resolve questions of causality.

The authors conclude that both serum urate level and its long-term longitudinal patterns were independently associated with rapid eGFR decline in this community cohort. They emphasize, however, that several key questions remain open. Whether repeated urate measurements add incremental value for clinical risk stratification requires prospective evaluation, and whether lowering or stabilizing urate can actually modify kidney risk remains unknown and would require randomized trials. Until such trials are conducted, the findings should be read as observational evidence of association, not as a prescription for urate-lowering treatment.

Subject of Research: Long-term serum urate trajectories and variability in relation to rapid kidney function decline in a community cohort

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

Article References: Hua, X., Fan, N., Zhu, P., Zhang, Y., Gao, S., & Wang, R. (2026). Association of serum urate trajectories and visit-to-visit variability with rapid egfr decline: a 5-year community cohort study. BMC Nephrology. https://doi.org/10.1186/s12882-026-05449-0

Image Credits: AI Generated

DOI: 10.1186/s12882-026-05449-0

Keywords: serum urate, eGFR decline, kidney function, cohort study, hyperuricemia, uric acid variability, chronic kidney disease, latent-class growth modeling, blood pressure, observational study, BMC Nephrology, risk factors