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Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Nature Reviews Nephrology volume 18, pages 259–268 (2022)Cite this article

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in more than 5% of hepatocytes in the absence of excessive alcohol consumption and other secondary causes of hepatic steatosis. In 2020, the more inclusive term metabolic (dysfunction)-associated fatty liver disease (MAFLD) — defined by broader diagnostic criteria — was proposed to replace the term NAFLD. The new terminology and revised definition better emphasize the pathogenic role of metabolic dysfunction and uses a set of definitive, inclusive criteria for diagnosis. Diagnosis of MAFLD is based on evidence of hepatic steatosis (as assessed by liver biopsy, imaging techniques or blood biomarkers and scores) in persons who are overweight or obese and have type 2 diabetes mellitus or metabolic dysregulation, regardless of the coexistence of other liver diseases or excessive alcohol consumption. The known association between NAFLD and chronic kidney disease (CKD) and our understanding that CKD can occur as a consequence of metabolic dysfunction suggests that individuals with MAFLD — who by definition have fatty liver and metabolic comorbidities — are at increased risk of CKD. In this Perspective article, we discuss the clinical associations between MAFLD and CKD, the pathophysiological mechanisms by which MAFLD may increase the risk of CKD and the potential drug treatments that may benefit both conditions.

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Fig. 1: Similarities and differences between NAFLD and MAFLD.
Fig. 2: PNPLA3 rs738409 polymorphism and potential shared pathogenic mechanisms in NAFLD and CKD.
Fig. 3: Potential mechanisms implicated in the gut–liver–kidney axis.

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Acknowledgements

The authors’ work was supported by grants from the National Natural Science Foundation of China (82070588, 82000690), High Level Creative Talents from the Department of Public Health in Zhejiang Province, Project of New Century 551 Talent Nurturing in Wenzhou and a Project of Science and Technology Development Fund in Wuxi (N20202001). D.-Q.S. is supported in part by grants from the Youth Research Project Fund from Wuxi Municipal Health Commission (Q201932), Top-notch Talents from Young and Middle-Age Health Care in Wuxi (BJ2020026). G.T. is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. C.D.B. is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK.

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Authors and Affiliations

  1. Department of Nephrology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Ting-Yao Wang

  2. Department of Nephrology, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, China

    Rui-Fang Wang, Zhi-Ying Bu & Dan-Qin Sun

  3. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

    Giovanni Targher

  4. Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK

    Christopher D. Byrne

  5. Affiliated Wuxi Clinical College of Nantong University, Wuxi, China

    Dan-Qin Sun

  6. NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Ming-Hua Zheng

  7. Institute of Hepatology, Wenzhou Medical University, Wenzhou, China

    Ming-Hua Zheng

  8. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China

    Ming-Hua Zheng

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  1. Ting-Yao Wang
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Contributions

R.-F.W., Z.-Y.B. and D.-Q.S. researched data for the article. T.-Y.W., G.T., C.D.B., D.-Q.S. and M.-H.Z. wrote the manuscript. All authors contributed substantially to the discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Dan-Qin Sun or Ming-Hua Zheng.

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Nature Reviews Nephrology thanks Manuel Praga, Yusuf Yilmaz and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Wang, TY., Wang, RF., Bu, ZY. et al. Association of metabolic dysfunction-associated fatty liver disease with kidney disease. Nat Rev Nephrol 18, 259–268 (2022). https://doi.org/10.1038/s41581-021-00519-y

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