Abstract
RATIONALE & OBJECTIVE: Evidence is limited regarding the associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with the development of nephrolithiasis. This study assessed the associations of NAFLD and MAFLD with the risk of incident nephrolithiasis using data from 2 cohort studies conducted in the People’s Republic of China and the United Kingdom.
STUDY DESIGN: Prospective cohort study.
SETTING & PARTICIPANTS: 26,490 participants without nephrolithiasis at baseline in the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH) and 294,577 participants in the UK Biobank.
EXPOSURE: Fatty liver diagnosed by abdominal ultrasonography in the TCLSIH and by the Hepatic Steatosis Index in the UK Biobank. NAFLD and MAFLD were defined according to standard clinical criteria in both cohorts.
OUTCOME: Nephrolithiasis was confirmed by ultrasonography in the TCLSIH and identified through ICD-10 and OPCS-4 in the UK Biobank.
ANALYTICAL APPROACH: Cox proportional hazards regression analysis was used to assess the relationship between exposures and incident nephrolithiasis.
RESULTS: The TCLSIH and the UK Biobank recorded 806 and 2,743 new cases of nephrolithiasis during a median follow-up period of 4 and 12 years, respectively. Participants in both cohorts showed a significantly increased risk of nephrolithiasis in the setting of NAFLD (TCLSIH: HR, 1.69 [95% CI, 1.46-1.95]; UK Biobank: HR, 1.66 [95% CI, 1.53-1.79]) and MAFLD (TCLSIH: HR, 1.79 [95% CI, 1.55-2.08]; UK Biobank: HR, 1.54 [95% CI, 1.42-1.66]) after multivariable adjustments.
LIMITATIONS: Observational nature limits causal inferences; generalizability limited outside of the cohorts studied; limited diagnostic approaches to detect nephrolithiasis; unavailability of stone composition data.
CONCLUSIONS: Both NAFLD and MAFLD are associated with a higher risk of nephrolithiasis. The results suggest that NAFLD/MAFLD and their associated metabolic conditions may represent modifiable risk factors for nephrolithiasis.
PLAIN-LANGUAGE SUMMARY: Evidence on the association between nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of nephrolithiasis remains limited. In this study, we assessed whether NAFLD or MAFLD were associated with an increased risk of developing nephrolithiasis by analyzing data from 2 large prospective cohorts in the People’s Republic of China and the United Kingdom. Our findings demonstrated that individuals with NAFLD or MAFLD had a significantly higher risk of incident nephrolithiasis later in life. This increased risk remained consistent across different age and sex groups. Our findings underscore the importance of liver health as a potential risk factor for nephrolithiasis.