Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than fatty liver or nonalcoholic fatty liver disease

Background: Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed.

Methods: We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or positive for urinary protein, over a 10-year period in 28 890 Japanese subjects who received annual health examinations. After exclusion of subjects with no data for abdominal ultrasonography and subjects with CKD at baseline, a total of 13 159 subjects (men 8581, women 4578; mean age 48 years) were recruited.

Results: The prevalence of FL, NAFLD and MAFLD was 34.6% (men 45.1%, women 15.1%), 32.8% (men 42.7%, women 14.5%) and 32.3% (men 42.4%, women 13.4%), respectively. During the 10-year follow-up period, 2163 subjects (men 1475, women 688) had new onset of CKD. Multivariable Cox proportional hazards model analyses showed that MAFLD [hazard ratio 1.12 (95% confidence interval 1.02-1.26); P = .027] but not FL or NAFLD was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD [continuous net reclassification improvement (NRI) 0.154, integrated discrimination improvement (IDI) 0.0024] to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI 0.138, IDI 0.0018) or NAFLD (NRI 0.132, IDI 0.0017).

Conclusions: MAFLD is modestly and independently associated with new onset of CKD and predicts the risk for development of CKD better than FL or NAFLD.