Combination of Hyperuricemia and Obesity Is an Independent Risk for CKD in the Young Population

Background: Recent studies have shown a significant relationship between hyperuricemia and kidney disease. However, managing serum uric acid (SUA) levels in incident chronic kidney disease (CKD) remains challenging. This study investigated the appropriate SUA management in incident CKD to prevent kidney dysfunction in the general population. Methods: This retrospective observational study included Japanese aged 20–60 years who underwent a health examination during 2009–2014. Participants with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria ≥1+ in 2009 were excluded. Incident CKD was defined as eGFR <60 mL/min/1.73 m2 or proteinuria 5 years later. Receiver operating characteristic (ROC) curve analysis was performed to determine the SUA cutoff value for incident CKD. The risk of incident CKD ( odds ratio [OR] and confidence interval [CI])was analyzed using logistic regression analysis. Propensity score matching based on the SUA cutoff value was performed to exclude biases related to participant covariances. Results: Of 16,708 recruited participants, 8,702 were eligible. Mean age, eGFR, and SUA were 41.4 years, 81.1 mL/min/1.73 m2, and 6.0 mg/dL, respectively. A total of 728 (8.4%) participants developed CKD. Based on the ROC analysis, the SUA cutoff value for incident CKD was 6.6 mg/dL. High SUA level (≥6.6 mg/dL) combined with obesity (body mass index ≥25 kg/m2) was a significant risk for incident CKD in participants aged <40 years (OR=2.18, 95% CI 1.10–4.31) but not if without obesity (OR=0.69, 95% CI 0.40–1.18). SUA level was significantly associated with obesity status (P=0.009). In participants aged ≥40 years, high SUA level was a risk factor for incident CKD, regardless of obesity status (OR 1.32, 95% CI 1.07–1.63). In participants aged <40 years with obesity and high SUA level, the difference in 5-year eGFR slope between participants with <6.6 mg/dl of SUA and those with ≥6.6 mg/dL (5-year later) was +0.80 mL/min/year (P=0.0002). Conclusion: In the population aged <40 years, SUA of ≥6.6 mg/dL combined with obesity was an independent risk for incident CKD 5 years later. Lowering SUA to <6.6 mg/dL may attenuate eGFR decline.