Development of Nephrolithiasis in Asymptomatic Hyperuricemia: A Cohort Study

BACKGROUND:Although the association between gout and nephrolithiasis is well known, the relationship between asymptomatic hyperuricemia and the development of nephrolithiasis is largely unknown. STUDY DESIGN:Cohort study. SETTING & PARTICIPANTS:239,331 Korean adults who underwent a health checkup examination during January 2002 to December 2014 and were followed up annually or biennially through December 2014. PREDICTOR:Baseline serum uric acid levels of participants. OUTCOME:The development of nephrolithiasis during follow-up. MEASUREMENTS:Nephrolithiasis is determined based on ultrasonographic findings. A parametric Cox model was used to estimate the adjusted HRs of nephrolithiasis according to serum uric acid level. RESULTS:During 1,184,653.8 person-years of follow-up, 18,777 participants developed nephrolithiasis (incidence rate, 1.6/100 person-years). Elevated uric acid level was significantly associated with increased risk for nephrolithiasis in a dose-response manner (P for trend < 0.001) in men. This dose-response association was not observed in women. In male participants, multivariable-adjusted HRs for incident nephrolithiasis comparing uric acid levels of 6.0 to 6.9, 7.0 to 7.9, 8.0 to 8.9, 9.0 to 9.9, and ≥10.0mg/dL with uric acid levels < 6.0mg/dL were 1.06 (95% CI, 1.02-1.11), 1.11 (95% CI, 1.05-1.16), 1.21 (95% CI, 1.13-1.29), 1.31 (95% CI, 1.17-1.46), and 1.72 (95% CI, 1.44-2.06), respectively. This association was observed in all clinically relevant subgroups and persisted even after adjustment for homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein level. LIMITATIONS:Dietary information and computed tomographic diagnosis of nephrolithiasis were unavailable. CONCLUSIONS:In this large cohort study, increased serum uric acid level was modestly and independently associated with increased risk for the development of nephrolithiasis in a dose-response manner in apparently healthy men.