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Therapeutic implications of shared mechanisms in non-alcoholic fatty liver disease and chronic kidney disease

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Abstract

The most common cause of liver disease worldwide is now non-alcoholic fatty liver disease (NAFLD). NAFLD refers to a spectrum of disease ranging from steatosis to non-alcoholic steatohepatitis, causing cirrhosis, and ultimately hepatocellular carcinoma. However, the impact of NAFLD is not limited to the liver. NAFLD has extra-hepatic consequences, most notably, cardiovascular and renal disease. NAFLD and chronic kidney disease share pathogenic mechanisms including insulin resistance, lipotoxicity, inflammation and oxidative stress. Not surprisingly, there has been a recent surge in efforts to manage NAFLD in an integrated way that not only protects the liver but also delays comorbidities such as chronic kidney disease. This concept of simultaneously addressing the main disease target and comorbidities is key to improve outcomes, as recently demonstrated by clinical trials of SGLT2 inhibitors and GLP1 receptor agonists in diabetes. HIF activators, already marketed in China, also have the potential to protect both liver and kidney, as suggested by preclinical data. This review concisely discusses efforts at identifying common pathogenic pathways between NAFLD and chronic kidney disease with an emphasis on potential paradigm shifts in diagnostic workup and therapeutic management.

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Acknowledgements

MK gratefully acknowledge use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.”AO research is supported by FIS PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT).

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Koc University School of Medicine, 34010, Istanbul, Turkey

    Mehmet Kanbay

  2. Department of Medicine, Koc University School of Medicine, Istanbul, Turkey

    Mustafa C. Bulbul & Sidar Copur

  3. Department of Internal Medicine, Division of Nephrology, Suleyman Demirel University School of Medicine, Isparta, Turkey

    Baris Afsar

  4. Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, USA

    Alan A. Sag

  5. Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, Iasi, Romania

    Dimitrie Siriopol, Silvia Badarau & Adrian Covic

  6. Department of Cardiology, Toranomon Hospital, Tokyo, Japan

    Masanari Kuwabara

  7. Dialysis Unit, School of Medicine, IIS-Fundacion Jimenez Diaz, Universidad Autónoma de Madrid, Avd. Reyes Católicos 2, 28040, Madrid, Spain

    Alberto Ortiz

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All authors contributed to: (1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and, (3) final approval of the version to be published.

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Correspondence to Mehmet Kanbay.

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Kanbay, M., Bulbul, M.C., Copur, S. et al. Therapeutic implications of shared mechanisms in non-alcoholic fatty liver disease and chronic kidney disease. J Nephrol 34, 649–659 (2021). https://doi.org/10.1007/s40620-020-00751-y

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