Gout flare burden as a marker of chronic kidney disease risk.

BACKGROUND

Gout is a common inflammatory arthritis with substantial cardiometabolic and renal comorbidity. Although hyperuricemia and baseline kidney function are established predictors of chronic kidney disease (CKD), the prognostic value of long-term gout flare frequency is unclear. This study aimed to examine the association between annual gout flare frequency and the risk of incident CKD.

METHODS

We conducted a large-scale retrospective cohort study using de-identified electronic health record data from the TriNetX Global Collaborative Research Network. Adults with at least one treated gout flare in 2017 and preserved baseline renal function (eGFR ≥ 60 mL/min/1.73 m²) were included. Exposure was defined by the annual frequency of treated gout flares. The primary outcome was incident CKD stage 3–5 or end-stage renal disease (ESRD). To minimize reverse causation, a 180-day lag period was applied before the start of follow-up. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for incident CKD over a 7-year follow-up period, adjusting for age, sex, comorbidities (hypertension, diabetes, heart disease, obesity), and urate-lowering therapy use.

RESULTS

Among 29,321 eligible adults, a higher annual gout flare frequency was independently associated with an increased risk of incident CKD in a graded, dose-dependent manner. Compared with individuals experiencing one flare per year, the risk of incident CKD was significantly higher among those with ≥ 5 flares per year, with aHRs ranging from approximately 1.20 to 1.46 across follow-up years. In contrast, experiencing two flares per year did not confer a statistically significant increase in risk relative to the reference group. Risk separation was evident by year 3 and persisted throughout the 7-year observation period.

CONCLUSIONS

Recurrent gout flares are associated with a progressively increased risk of incident CKD, suggesting that flare frequency serves as a pragmatic, patient-centered prognostic marker for long-term renal risk assessment. These findings underscore the importance of optimizing flare prevention and urate-lowering strategies in high-risk populations to potentially mitigate adverse renal outcomes.