Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease

A Systematic Review and Meta-analysis

Giovanni Musso, Roberto Gambino, James H. Tabibian, Mattias Ekstedt, Stergios Kechagias, Masahide Hamaguchi, Rolf Hultcrantz, Hannes Hagström, Seung Kew Yoon, Phunchai Charatcharoenwitthaya, Jacob George, Francisco Barrera, Svanhildur Haflidadóttir, Einar Stefan Björnsson, Matthew J. Armstrong, Laurence J. Hopkins, Xin Gao, Sven Francque, An Verrijken, Yusuf Yilmaz & 13 others Keith Lindor, Michael Charlton, Robin Haring, Markus M. Lerch, Rainer Rettig, Henry Völzke, Seungho Ryu, Guolin Li, Linda L. Wong, Mariana Machado, Helena Cortez-Pinto, Kohichiroh Yasui, Maurizio Cassader

Research output: Contribution to journalArticle

171 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1001680
JournalPLoS Medicine
Volume11
Issue number7
DOIs
StatePublished - 2014
Externally publishedYes

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Chronic Renal Insufficiency
Meta-Analysis
Odds Ratio
Biochemistry
Histology
Fibrosis
Cross-Sectional Studies
Non-alcoholic Fatty Liver Disease
Abdominal Obesity
Incidence
Fatty Liver
Glomerular Filtration Rate
Proteinuria
Population
Observational Studies
Renal Insufficiency
Longitudinal Studies
Insulin Resistance
Homeostasis
Cardiovascular Diseases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Musso, G., Gambino, R., Tabibian, J. H., Ekstedt, M., Kechagias, S., Hamaguchi, M., ... Cassader, M. (2014). Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis. PLoS Medicine, 11(7), [e1001680]. https://doi.org/10.1371/journal.pmed.1001680

Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease : A Systematic Review and Meta-analysis. / Musso, Giovanni; Gambino, Roberto; Tabibian, James H.; Ekstedt, Mattias; Kechagias, Stergios; Hamaguchi, Masahide; Hultcrantz, Rolf; Hagström, Hannes; Yoon, Seung Kew; Charatcharoenwitthaya, Phunchai; George, Jacob; Barrera, Francisco; Haflidadóttir, Svanhildur; Björnsson, Einar Stefan; Armstrong, Matthew J.; Hopkins, Laurence J.; Gao, Xin; Francque, Sven; Verrijken, An; Yilmaz, Yusuf; Lindor, Keith; Charlton, Michael; Haring, Robin; Lerch, Markus M.; Rettig, Rainer; Völzke, Henry; Ryu, Seungho; Li, Guolin; Wong, Linda L.; Machado, Mariana; Cortez-Pinto, Helena; Yasui, Kohichiroh; Cassader, Maurizio.

In: PLoS Medicine, Vol. 11, No. 7, e1001680, 2014.

Research output: Contribution to journalArticle

Musso, G, Gambino, R, Tabibian, JH, Ekstedt, M, Kechagias, S, Hamaguchi, M, Hultcrantz, R, Hagström, H, Yoon, SK, Charatcharoenwitthaya, P, George, J, Barrera, F, Haflidadóttir, S, Björnsson, ES, Armstrong, MJ, Hopkins, LJ, Gao, X, Francque, S, Verrijken, A, Yilmaz, Y, Lindor, K, Charlton, M, Haring, R, Lerch, MM, Rettig, R, Völzke, H, Ryu, S, Li, G, Wong, LL, Machado, M, Cortez-Pinto, H, Yasui, K & Cassader, M 2014, 'Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis', PLoS Medicine, vol. 11, no. 7, e1001680. https://doi.org/10.1371/journal.pmed.1001680
Musso, Giovanni ; Gambino, Roberto ; Tabibian, James H. ; Ekstedt, Mattias ; Kechagias, Stergios ; Hamaguchi, Masahide ; Hultcrantz, Rolf ; Hagström, Hannes ; Yoon, Seung Kew ; Charatcharoenwitthaya, Phunchai ; George, Jacob ; Barrera, Francisco ; Haflidadóttir, Svanhildur ; Björnsson, Einar Stefan ; Armstrong, Matthew J. ; Hopkins, Laurence J. ; Gao, Xin ; Francque, Sven ; Verrijken, An ; Yilmaz, Yusuf ; Lindor, Keith ; Charlton, Michael ; Haring, Robin ; Lerch, Markus M. ; Rettig, Rainer ; Völzke, Henry ; Ryu, Seungho ; Li, Guolin ; Wong, Linda L. ; Machado, Mariana ; Cortez-Pinto, Helena ; Yasui, Kohichiroh ; Cassader, Maurizio. / Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease : A Systematic Review and Meta-analysis. In: PLoS Medicine. 2014 ; Vol. 11, No. 7.
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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.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.",
author = "Giovanni Musso and Roberto Gambino and Tabibian, {James H.} and Mattias Ekstedt and Stergios Kechagias and Masahide Hamaguchi and Rolf Hultcrantz and Hannes Hagstr{\"o}m and Yoon, {Seung Kew} and Phunchai Charatcharoenwitthaya and Jacob George and Francisco Barrera and Svanhildur Haflidad{\'o}ttir and Bj{\"o}rnsson, {Einar Stefan} and Armstrong, {Matthew J.} and Hopkins, {Laurence J.} and Xin Gao and Sven Francque and An Verrijken and Yusuf Yilmaz and Keith Lindor and Michael Charlton and Robin Haring and Lerch, {Markus M.} and Rainer Rettig and Henry V{\"o}lzke and Seungho Ryu and Guolin Li and Wong, {Linda L.} and Mariana Machado and Helena Cortez-Pinto and Kohichiroh Yasui and Maurizio Cassader",
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TY - JOUR

T1 - Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease

T2 - 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 - Haflidadóttir, 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

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

PY - 2014

Y1 - 2014

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.

AB - 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.

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