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Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis

Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis
Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis
Background Recent studies examined the prognostic impact of nonalcoholic fatty liver disease (NAFLD) on the risk of incident chronic kidney disease (CKD). However, the extent to which NAFLD may confer risk of incident CKD is uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident CKD.Methods We searched PubMed, Scopus and Web of Science from January 1, 2000 to August 31, 2017 using pre-defined keywords to identify large observational cohort studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by biochemistry, fatty liver index or ultrasonography. No studies with biopsy-proven NAFLD were available for the analysis. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.Results A total of 9 observational studies with 96,595 adult individuals (34.1% with NAFLD) of predominantly Asian descent, and 4653 cases of incident CKD stage ≥ 3 (i.e., defined as occurrence of estimated glomerular filtration rate < 60 ml/min/1.73 m2, with or without accompanying overt proteinuria) over a median period of 5.2 years were included in the final analysis. Patients with NAFLD had a significantly higher risk of incident CKD than those without NAFLD (random-effects hazard ratio [HR] 1.37, 95% CI 1.20–1.53; I2 = 33.5%). Patients with more ‘severe’ NAFLD (according to ultrasonography and non-invasive fibrosis markers) were also more likely to develop incident CKD (n = 2 studies; random-effects HR 1.50, 95% CI 1.25–1.74; I2 = 0%); this risk appeared to be even greater among those with ultrasound-diagnosed NAFLD and a high-intermediate NAFLD fibrosis score (n = 1 study; random-effects HR 1.59, 95% CI 1.31–1.93). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.Conclusions This largest and most updated meta-analysis to date shows that NAFLD (detected by biochemistry, fatty liver index or ultrasonography) is associated with a nearly 40% increase in the long-term risk of incident CKD. However, the observational nature of the eligible studies does not allow for proving causality. Our findings pave the way for future large, prospective, histologically-based studies.
0026-0495
64-76
Mantovani, A.
e52e3bfc-9e58-40e8-a516-77ef85802d7d
Zaza, G.
e42b772a-d2d3-4fee-afb6-24f575a31348
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Lonardo, A.
1b2cd6b6-c950-4a8c-9830-d63df3924b96
Zoppini, G.
ec08fd28-18a3-4012-89ce-e11cb6537deb
Bonor, E.
b67b9149-5b33-49b0-8f59-7631d43b86f8
Targher, G.
5a842bd2-91c4-4063-b639-da6c681f3698
Mantovani, A.
e52e3bfc-9e58-40e8-a516-77ef85802d7d
Zaza, G.
e42b772a-d2d3-4fee-afb6-24f575a31348
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Lonardo, A.
1b2cd6b6-c950-4a8c-9830-d63df3924b96
Zoppini, G.
ec08fd28-18a3-4012-89ce-e11cb6537deb
Bonor, E.
b67b9149-5b33-49b0-8f59-7631d43b86f8
Targher, G.
5a842bd2-91c4-4063-b639-da6c681f3698

Mantovani, A., Zaza, G., Byrne, C., Lonardo, A., Zoppini, G., Bonor, E. and Targher, G. (2018) Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism, 79, 64-76. (doi:10.1016/j.metabol.2017.11.003).

Record type: Article

Abstract

Background Recent studies examined the prognostic impact of nonalcoholic fatty liver disease (NAFLD) on the risk of incident chronic kidney disease (CKD). However, the extent to which NAFLD may confer risk of incident CKD is uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident CKD.Methods We searched PubMed, Scopus and Web of Science from January 1, 2000 to August 31, 2017 using pre-defined keywords to identify large observational cohort studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by biochemistry, fatty liver index or ultrasonography. No studies with biopsy-proven NAFLD were available for the analysis. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.Results A total of 9 observational studies with 96,595 adult individuals (34.1% with NAFLD) of predominantly Asian descent, and 4653 cases of incident CKD stage ≥ 3 (i.e., defined as occurrence of estimated glomerular filtration rate < 60 ml/min/1.73 m2, with or without accompanying overt proteinuria) over a median period of 5.2 years were included in the final analysis. Patients with NAFLD had a significantly higher risk of incident CKD than those without NAFLD (random-effects hazard ratio [HR] 1.37, 95% CI 1.20–1.53; I2 = 33.5%). Patients with more ‘severe’ NAFLD (according to ultrasonography and non-invasive fibrosis markers) were also more likely to develop incident CKD (n = 2 studies; random-effects HR 1.50, 95% CI 1.25–1.74; I2 = 0%); this risk appeared to be even greater among those with ultrasound-diagnosed NAFLD and a high-intermediate NAFLD fibrosis score (n = 1 study; random-effects HR 1.59, 95% CI 1.31–1.93). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.Conclusions This largest and most updated meta-analysis to date shows that NAFLD (detected by biochemistry, fatty liver index or ultrasonography) is associated with a nearly 40% increase in the long-term risk of incident CKD. However, the observational nature of the eligible studies does not allow for proving causality. Our findings pave the way for future large, prospective, histologically-based studies.

Text NAFLD_incident CKD risk_revised_tracked_R1 - Accepted Manuscript
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Text Table S1_Excluded eligible studies_R1 - Accepted Manuscript
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Text Table S2_NOS_CKD_R1 - Accepted Manuscript
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Text Figure 1_by diagnosis - Accepted Manuscript
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Text Figure 3_by diabetes - Accepted Manuscript
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Text Figure 4_by country - Accepted Manuscript
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Text Figure 5_by severity - Accepted Manuscript
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Text Figure S1_PRISMA Flow chart_R1 - Accepted Manuscript
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Text Figure S2_Funnel plot - Accepted Manuscript
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Accepted/In Press date: 4 November 2017
e-pub ahead of print date: 11 November 2017
Published date: February 2018

Identifiers

Local EPrints ID: 415394
URI: https://eprints.soton.ac.uk/id/eprint/415394
ISSN: 0026-0495
PURE UUID: fb7a5f03-94f5-48b1-89f9-74f13595ae78
ORCID for C. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 09 Nov 2017 17:30
Last modified: 06 Feb 2018 17:30

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Contributors

Author: A. Mantovani
Author: G. Zaza
Author: C. Byrne ORCID iD
Author: A. Lonardo
Author: G. Zoppini
Author: E. Bonor
Author: G. Targher

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