title: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Gradenigo Hospital, University of Turin, Turin, Italy.
authors: Giovanni
authors: G
authors: Musso
authors: Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors: Roberto
authors: R
authors: Gambino
authors: Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.
authors: James H
authors: JH
authors: Tabibian
authors: Division of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden.
authors: Mattias
authors: M
authors: Ekstedt
authors: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors: Stergios
authors: S
authors: Kechagias
authors: Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors: Masahide
authors: M
authors: Hamaguchi
authors: Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Rolf
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authors: Hultcrantz
authors: Departments of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Hannes
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authors: Hagström
authors: Division of Hepato-Gastroenterology, Department of Internal Medicine, Kangnam St. Mary Hospital, Catholic University Medical College, Seoul, Korea.
authors: Seung Kew
authors: SK
authors: Yoon
authors: Division of Gastroenterology, Medicine Department, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand.
authors: Phunchai
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authors: Charatcharoenwitthaya
authors: Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
authors: Jacob
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authors: George
authors: Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, New South Wales, Australia.
authors: Francisco
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authors: Barrera
authors: Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland.
authors: Svanhildur
authors: S
authors: Hafliðadóttir
authors: Dept of Gastroenterology and Hepatology, Landspitali University Hospital, Hringbrau, Reykjavik, Iceland.
authors: Einar Stefan
authors: ES
authors: Björnsson
authors: Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Matthew J
authors: MJ
authors: Armstrong
authors: Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
authors: Laurence J
authors: LJ
authors: Hopkins
authors: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Xin
authors: X
authors: Gao
authors: Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
authors: Sven
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authors: Francque
authors: Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
authors: An
authors: A
authors: Verrijken
authors: Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
authors: Yusuf
authors: Y
authors: Yilmaz
authors: Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Keith D
authors: KD
authors: Lindor
authors: Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Michael
authors: M
authors: Charlton
authors: Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
authors: Robin
authors: R
authors: Haring
authors: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors: Markus M
authors: MM
authors: Lerch
authors: Institute of Physiology, Ernst-Moritz-Arndt-University Medicine Greifswald, Karlsburg, Germany.
authors: Rainer
authors: R
authors: Rettig
authors: Institute for Community Medicine, Ernst-Moritz-Arndt University Medicine Greifswald, Greifswald, Germany.
authors: Henry
authors: H
authors: Völzke
authors: Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
authors: Seungho
authors: S
authors: Ryu
authors: College of Life Sciences, Hunan Normal University, Changsha, China.
authors: Guolin
authors: G
authors: Li
authors: John A. Burns School of Medicine at University of Hawaii, Transplant Institute, Hawaii Medical Center, Honolulu, Hawaii, United States of America.
authors: Linda L
authors: LL
authors: Wong
authors: Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal.
authors: Mariana
authors: M
authors: Machado
authors: Department of Gastroenterology, University Hospital of Santa Maria, Institute of Molecular Medicine, Lisbon, Portugal.
authors: Helena
authors: H
authors: Cortez-Pinto
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan.
authors: Kohichiroh
authors: K
authors: Yasui
authors: Dept. of Medical Sciences, San Giovanni Battista Hospital, University of Turin, Turin, Italy.
authors: Maurizio
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authors: Cassader
mesh_terms: D006801:Humans; D015994:Incidence; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000209:etiology; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors