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 ≥10.0 mg/dL with uric acid levels < 6.0 mg/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. Although the association between gout and nephrolithiasis is well known, the relationship between asymptomatic hyperuricemia and the development of nephrolithiasis is largely unknown. Cohort study. 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. Baseline serum uric acid levels of participants. The development of nephrolithiasis during follow-up. 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. 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 ≥10.0 mg/dL with uric acid levels < 6.0 mg/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. Dietary information and computed tomographic diagnosis of nephrolithiasis were unavailable. 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.