An evaluation of longitudinal changes in serum uric acid levels and associated risk of cardio-metabolic events and renal function decline in gout

OBJECTIVE: Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. METHODS: An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement ≥6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (≥30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). RESULTS: Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51–1.75) for DM, 0.77 (0.70–0.84) for CVD, and 4.32 (4.14–4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of <6 mg/dl in this population, was 1.04 (0.92–1.17) for DM, 1.07 (0.89–1.29) for CVD, and 0.85 (0.78–0.92) for renal function decline. CONCLUSIONS: Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD.