The association between steatotic liver disease and chronic kidney disease: a meta-analysis and Mendelian randomization study highlighting metabolic comorbidities

Steatotic liver disease (SLD)-a term encompassing nonalcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and metabolic dysfunction-associated steatotic liver disease (MASLD)-and chronic kidney disease (CKD) are major global health concerns. Metabolic factors, including obesity, type 2 diabetes, hypertension, and dyslipidemia, are integral to the definitions of MAFLD and MASLD and may confound their association with CKD. This study aimed to update a meta-analysis on the association between SLD and CKD risk and to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal roles of SLD and metabolic factors in CKD. We systematically searched PubMed, Embase, and Web of Science up to November 5, 2024, for eligible studies. Random-effects models were used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Two-sample MR was performed using the inverse-variance weighted (IVW) method as the primary model, with additional methods applied for sensitivity analyses. A total of 34 studies involving 3,783,136 participants were included in the meta-analysis. The results demonstrated significant positive associations between MAFLD, NAFLD, and MASLD with CKD (MAFLD: OR 1.41 [1.07-1.84], RR 1.64 [1.39-1.94], HR 1.64 [1.39-1.94]; NAFLD: OR 1.19 [1.08-1.31], RR 1.66 [1.45-1.91], HR 1.43 [1.31-1.55]; MASLD: HR 1.34 [1.08-1.67]). These findings support a significant association between SLD (MAFLD, NAFLD, and MASLD) and an increased risk of CKD. However, Mendelian randomization (MR) analysis found no causal effect of SLD on CKD risk. In contrast, genetically predicted metabolic factors-including body mass index (BMI), waist circumference, type 2 diabetes, systolic and diastolic blood pressure, triglycerides, and high-density lipoprotein cholesterol-were significantly associated with an increased CKD risk. These findings suggest that metabolic dysfunction, rather than SLD itself, may be the main driver of CKD risk. This underscores the clinical importance of early screening and intervention for metabolic health in patients with SLD to reduce the burden of CKD.