Non-alcoholic fatty liver disease and the development of nephrolithiasis: A cohort study

BACKGROUND Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation or precursor of metabolic syndrome, may increase nephrolithiasis, a renal manifestation of insulin resistance, but the prospective association between NAFLD and incident nephrolithiasis has not been evaluated. We examined the association of NAFLD with the development of nephrolithiasis in a large cohort of Korean men and women. METHODS We performed a cohort study of 208,578 Korean adults who underwent a health checkup examination between January 2002 and December 2014 and were followed-up annually or biennially through December 2014. NAFLD was defined as the presence of fatty liver in the absence of excessive alcohol use or other identifiable causes. Fatty liver and nephrolithiasis were determined based on ultrasonographic findings. We used a parametric Cox model to estimate the adjusted hazard ratios (HRs) of nephrolithiasis according to the presence of NAFLD. RESULTS During 1,054,887.6 person-year of follow-up, 16,442 participants developed nephrolithiasis. After adjusting for age, center, year of screening exam, smoking status, alcohol intake, physical activity, education level, body mass index, history of hypertension and diabetes, HOMA-IR, uric acid and C-reactive protein, male participants with NAFLD had a significantly increased risk of nephrolithiasis than those without NAFLD (adjusted HR 1.17, 95% CI 1.06-1.30). However, no association between NAFLD and nephrolithiasis was observed in women (adjusted HR 0.97, 95% CI 0.81-1.16). CONCLUSIONS In this large cohort study of young and middle-aged Koreans, NAFLD was significantly associated with an increased incidence of nephrolithiasis in men but not in women.