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Study Concludes Greater Focus Needed on MAFLD Due to CKD Risk Association


Investigators confirmed an association between fatty liver disease related to metabolic dysfunction (MAFLD) and chronic kidney disease (CKD), and stressed a greater focus on treating MAFLD is needed to help manage risks.

In a recent study, metabolic dysfunction-associated fatty liver disease (MAFLD) was found to be associated with risk of chronic kidney disease (CKD), suggesting a greater focus on treating MAFLD as a preventative measure is needed.

The retrospective cross-sectional study, published in the Journal of Diabetes Investigation, clarified that although patients with MAFLD were at an increased risk of CKD compared with patients without FLD, patients with FLD without metabolic dysfunction (MD) were not at risk of CKD.

In the past, nonalcoholic FLD (NAFLD) was used to convey the high risk of hepatic disease progression because of its close relationship with CKD. But because the definition of NAFLD requires the exclusion of heavy drinking and other chronic liver diseases, MAFLD is hypothesized to be a more practical and precise definition for high risk. However, results from previous cross-sectional studies assessing the connection between MAFLD and CKD have been inconsistent.

The NAFLD in Gifu Area, Longitudinal Analysis (NAGALA) study comprised of patients enrolled in a medical health checkup program at Asahi University Hospital in Japan between January 2004 and December 2014. Data were collected from the participants' medical history and lifestyle factors were reported via self-completed questionnaires. MAFLD was defined by the presence of fatty liver disease along with either being overweight or obese, having type 2 diabetes, or having metabolic dysregulation without being overweight.

Among the 27,941 individuals originally identified, 27,371 were included in the cross-sectional study and 16,938 were included in the retrospective cohort study. The average (SD) age of the cohort was 45.7 (10.1) years and 59.0% were men.

In the cross-sectional study, 14.1% of the patients had CKD, 49.0% had MD, and 23.1% had FLD. Additionally, 48.7% patients did not have FLD or MD, 28.2% had MD but not FLD, 2.3% had non-MD FLD, and 20.8% had MAFLD. The group with MAFLD was at a risk of CKD (adjusted OR [aOR], 1.83; 95% CI, 1.66-2.01, P < .001) compared with the non-FLD group. However, the group with FLD without MD was not associated with risk of CKD (aOR, 1.02; 95% CI, 0.79-1.33, P = .868).

For the retrospective cohort analysis, 46.3% had MD and 22.0% had FLD, with 19.3% of the cohort having MAFLD. During the median 4.6-year follow-up, 16.5% of patients developed CKD. The incidence rate of CKD cases per 1000 person-years was 21.0 for the group that did not have FLD or MD, 26.1 for the group with FLD but not MD, and 31.1 for the MAFLD group.

Similarly to the cross-sectional analysis, the patients with MAFLD were at risk of incident CKD compared with the patients that had neither FLD or MD (adjusted HR [aHR], 1.30; 95% CI, 1.14-1.36; P < .001). However, the patients with FLD but not MD were not at risk of developing CKD (aHR, 1.11; 95% CI, 0.85-1.41; P = .433).

Investigators suggested the link between MAFLD and CKD may be insulin resistance, which is known to contribute to CKD progression. Metabolic dysfunction is also associated with insulin resistance.

The study had several limitations, including the lack of liver biopsy for FLD diagnosis, limited generalizability, lack of a definition for proteinuria, and the lack of data on insulin, high sensitivity C-reactive protein, and standard oral glucose tolerance tests.


Hashimoto Y, Hamaguchi M, Okamura T, et al. Metabolic associated fatty liver disease is a risk factor for chronic kidney disease. J Diabetes Investig. 2022;13:308-316. doi:10.1111/jdi.13678

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