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Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis.
Metabolism. 2018 02; 79:64-76.M

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 1year, 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<60ml/min/1.73m2, with or without accompanying overt proteinuria) over a median period of 5.2years 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.

Authors+Show Affiliations

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.Renal Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, UK.Department of Internal Medicine and Metabolic Diseases, Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Modena, Italy.Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address: giovanni.targher@univr.it.

Pub Type(s)

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

Language

eng

PubMed ID

29137912

Citation

Mantovani, Alessandro, et al. "Nonalcoholic Fatty Liver Disease Increases Risk of Incident Chronic Kidney Disease: a Systematic Review and Meta-analysis." Metabolism: Clinical and Experimental, vol. 79, 2018, pp. 64-76.
Mantovani A, Zaza G, Byrne CD, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2018;79:64-76.
Mantovani, A., Zaza, G., Byrne, C. D., Lonardo, A., Zoppini, G., Bonora, E., & Targher, G. (2018). Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism: Clinical and Experimental, 79, 64-76. https://doi.org/10.1016/j.metabol.2017.11.003
Mantovani A, et al. Nonalcoholic Fatty Liver Disease Increases Risk of Incident Chronic Kidney Disease: a Systematic Review and Meta-analysis. Metabolism. 2018;79:64-76. PubMed PMID: 29137912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. AU - Mantovani,Alessandro, AU - Zaza,Gianluigi, AU - Byrne,Christopher D, AU - Lonardo,Amedeo, AU - Zoppini,Giacomo, AU - Bonora,Enzo, AU - Targher,Giovanni, Y1 - 2017/11/11/ PY - 2017/08/30/received PY - 2017/11/02/revised PY - 2017/11/04/accepted PY - 2017/11/16/pubmed PY - 2018/10/23/medline PY - 2017/11/16/entrez KW - CKD risk KW - Meta-analysis KW - NAFLD SP - 64 EP - 76 JF - Metabolism: clinical and experimental JO - Metabolism VL - 79 N2 - 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 1year, 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<60ml/min/1.73m2, with or without accompanying overt proteinuria) over a median period of 5.2years 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. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/29137912/Nonalcoholic_fatty_liver_disease_increases_risk_of_incident_chronic_kidney_disease:_A_systematic_review_and_meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(17)30306-2 DB - PRIME DP - Unbound Medicine ER -