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Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

Abstract

BACKGROUND

Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.

METHODS AND FINDINGS

English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.

CONCLUSION

The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.

Links

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  • Authors+Show Affiliations

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    Gradenigo Hospital, University of Turin, Turin, Italy.

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    Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.

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    Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.

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    Division of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden.

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    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

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    Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.

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    Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

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    Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

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    Division of Hepato-Gastroenterology, Department of Internal Medicine, Kangnam St. Mary Hospital, Catholic University Medical College, Seoul, Korea.

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    Division of Gastroenterology, Medicine Department, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand.

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    Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.

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    Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.

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    Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland.

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    Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland.

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    Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.

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    Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.

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    Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.

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    Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.

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    Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.

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    Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.

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    Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.

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    Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.

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    Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.

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    Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.

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    Institute of Physiology, Ernst-Moritz-Arndt-University Medicine Greifswald, Karlsburg, Germany.

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    Institute for Community Medicine, Ernst-Moritz-Arndt University Medicine Greifswald, Greifswald, Germany.

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    Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.

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    College of Life Sciences, Hunan Normal University, Changsha, China.

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    John A. Burns School of Medicine at University of Hawaii, Transplant Institute, Hawaii Medical Center, Honolulu, Hawaii, United States of America.

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    Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal.

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    Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal.

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    Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan.

    Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.

    Source

    PLoS medicine 11:7 2014 Jul pg e1001680

    MeSH

    Humans
    Incidence
    Non-alcoholic Fatty Liver Disease
    Regression Analysis
    Renal Insufficiency, Chronic
    Risk Factors

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    25050550

    Citation

    TY - JOUR T1 - Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. AU - Musso,Giovanni, AU - Gambino,Roberto, AU - Tabibian,James H, AU - Ekstedt,Mattias, AU - Kechagias,Stergios, AU - Hamaguchi,Masahide, AU - Hultcrantz,Rolf, AU - Hagström,Hannes, AU - Yoon,Seung Kew, AU - Charatcharoenwitthaya,Phunchai, AU - George,Jacob, AU - Barrera,Francisco, AU - Hafliðadóttir,Svanhildur, AU - Björnsson,Einar Stefan, AU - Armstrong,Matthew J, AU - Hopkins,Laurence J, AU - Gao,Xin, AU - Francque,Sven, AU - Verrijken,An, AU - Yilmaz,Yusuf, AU - Lindor,Keith D, AU - Charlton,Michael, AU - Haring,Robin, AU - Lerch,Markus M, AU - Rettig,Rainer, AU - Völzke,Henry, AU - Ryu,Seungho, AU - Li,Guolin, AU - Wong,Linda L, AU - Machado,Mariana, AU - Cortez-Pinto,Helena, AU - Yasui,Kohichiroh, AU - Cassader,Maurizio, Y1 - 2014/07/22/ PY - 2014/7//ecollection PY - 2013/7/15/received PY - 2014/6/12/accepted PY - 2014/7/22/epublish PY - 2014/7/23/entrez PY - 2014/7/23/pubmed PY - 2015/10/10/medline SP - e1001680 EP - e1001680 JF - PLoS medicine JO - PLoS Med. VL - 11 IS - 7 N2 - BACKGROUND: Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION: The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/25050550/full_citation L2 - http://dx.plos.org/10.1371/journal.pmed.1001680 ER -