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Original research
Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis
  1. Alessandro Mantovani1,
  2. Graziana Petracca1,
  3. Giorgia Beatrice1,
  4. Alessandro Csermely1,
  5. Amedeo Lonardo2,
  6. Jörn M Schattenberg3,
  7. Herbert Tilg4,
  8. Christopher D Byrne5,
  9. Giovanni Targher1
  1. 1 Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Veneto, Italy
  2. 2 Internal Medicine, University of Modena and Reggio Emilia Faculty of Medicine and Surgery, Modena, Emilia-Romagna, Italy
  3. 3 Department of Internal Medicine I, University Medical Center Mainz Department of Internal Medicine 1, Mainz, Rheinland-Pfalz, Germany
  4. 4 Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, University of Innsbruck, Innsbruck, Tirol, Austria
  5. 5 University of Southampton Faculty of Medicine, Southampton, Southampton, UK
  1. Correspondence to Professor Giovanni Targher, Endocrinology and Metabolism, University of Verona Department of Medicine, 37129 Verona, Italy; giovanni.targher{at}


Objective Studies reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased risk of chronic kidney disease (CKD). However, whether this risk changes with increasing severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CKD.

Design We systematically searched PubMed, Web of Science and Scopus from January 2000 to August 2020 using predefined keywords to identify observational studies with a follow-up duration of ≥1 year, in which NAFLD was diagnosed by blood biomarkers/scores, International Classification of Diseases codes, imaging techniques or biopsy. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling.

Results 13 studies with 1 222 032 individuals (28.1% with NAFLD) and 33 840 cases of incident CKD stage ≥3 (defined as estimated glomerular filtration rate <60 mL/min/1.73 m2, with or without accompanying overt proteinuria) over a median follow-up of 9.7 years were included. NAFLD was associated with a moderately increased risk of incident CKD (n=10 studies; random-effects HR 1.43, 95% CI 1.33 to 1.54; I 2=60.7%). All risks were independent of age, sex, obesity, hypertension, diabetes and other conventional CKD risk factors. Sensitivity analyses did not alter these findings. Funnel plot did not reveal any significant publication bias.

Conclusion This large and updated meta-analysis indicates that NAFLD is significantly associated with a~1.45-fold increased long-term risk of incident CKD stage ≥3. Further studies are needed to examine the association between the severity of NAFLD and risk of incident CKD.

  • nonalcoholic steatohepatitis
  • fatty liver
  • meta-analysis

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Contributors Study concept and design: AM and GT; acquisition of data: AM, GP, GB, AC, GT; statistical analysis of data: AM; analysis and interpretation of data: AM and GT; drafting of the manuscript: GT; critical revision of the manuscript for important intellectual content: AL, JMS, HT and CDB.

  • Funding GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. CDB is supported in part by the Southampton National Institute for Health Research (NIHR) Biomedical Research Centre.

  • Competing interests JMS has acted as consultant for BMS, Boehringer Ingelheim, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Pfizer, Roche and has received research funding from Gilead Sciences. All other authors have no potential conflicts of interest to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.