Background/Purpose: Gout patients have an increased risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD); however, it is not known whether this risk is modifiable by reducing levels of serum uric acid (SUA). Therefore, we aimed to evaluate the association between changes in SUA levels over time and the risk of incident T2DM, CVD, and renal function insufficiency in gout patients.

Methods: We designed an observational cohort study among gout patients aged > 40 years using data from Optum Clinformatics database with available laboratory results (2004-2015). Index date was defined as the first SUA measurement ≥6.8 mg/dl after 6 months of continuous health plan coverage, ≥1 gout diagnosis and no use of urate lowering treatment during this time. The exposure of interest was change in SUA level, which measured as a cumulative variable updated monthly. Three separate outcomes were assessed during the post-index period: 1) incident T2DM, 2) incident CVD (a composite endpoint of myocardial infarction, stroke, or coronary revascularization), 3) renal insufficiency (reduction in the estimated glomerular filtration rate of ≥ 30% from baseline). Hazard ratios (HR) and 95% confidence intervals (CI) were derived using marginal structural models with stabilized inverse probability treatment weights accounting for baseline confounders including age, gender, hyperlipidemia, hypertension, and >20 other medical conditions and medication use as well as >10 time-varying confounders including serum creatinine, blood urea nitrogen, glycated hemoglobin, and urate lowering drugs.

Results: Among 26,341 patients with gout, the average age was 62 and 75% were men. The median baseline SUA was 8.6 mg/dl (interquartile range (IQR) 7.7 to 9.5) and the median level of SUA reduction over an average follow-up of 33 months was 1 mg/dl (IQR: 0 to 2.7). The incidence rates/100 person-years (95% CI) were 1.63 (1.51-1.75) for T2DM, 0.77 (0.70-0.84) for CVD, and 4.32 (4.14-4.49) for renal insufficiency. The HR (95% CI) per 3 mg/dl reduction in SUA was 1.07 (0.91-1.24) for T2DM, 1.01 (0.81-1.27) for CVD, and 0.89 (0.81-0.98) for renal insufficiency.

Conclusion:   Reduction in SUA in patients with gout may be associated with a reduced risk of renal insufficiency, but we did not find an association with T2DM or CAD. These findings suggest that aggressive SUA lowering approaches may slow renal disease progression but it is less clear whether such approaches will reduce the risk of T2DM or CAD in gout patients.

Table- Association between cumulative changes in uric acid over time and outcome events of interest in gout patients, Optum Clinformatics data 2004-2015