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Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study

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Abstract

Background

A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD.

Methods

In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60 mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors.

Results

FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data.

Conclusions

Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.

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Acknowledgements

The authors thank the participants in the FKR Study, and the members of the FKR Study Group: Toshiaki Nakano, Takanari Kitazono, Toshiharu Ninomiya, Kumiko Torisu, Shigeru Tanaka, Akihiro Tsuchimoto, Shunsuke Yamada, Hiroto Hiyamuta (Kyushu University); Satoru Fujimi, Hideki Hirakata (Fukuoka Renal Clinic); Tetsuhiko Yoshida, Takashi Deguchi (Hamanomachi Hospital); Dai Matsuo (Munakata Medical Association Hospital); Hideki Yotsueda (Harasanshin Hospital); Akinori Nagashima (Japanese Red Cross Karatsu Hospital); Taihei Yanagida (Steel Memorial Yawata Hospital); Shotaro Onaka (Tagawa Municipal Hospital); Tadashi Hirano (Hakujyuji Hospital); Tohru Mizumasa (Kyushu Central Hospital); Hidetoshi Kanai, Kenji Harada (Kokura Memorial Hospital); Koji Mitsuiki, Keita Takae (Japanese Red Cross Fukuoka Hospital); Masaru Nakayama (National Kyushu Medical Center); Yusuke Kuroki, Hiroshi Nagae (National Fukuoka-Higashi Medical Center); Kiichiro Fujisaki (Iizuka Hospital); Kazuhiko Tsuruya (Nara Medical University); Masaharu Nagata (Shin-eikai Hospital); Ritsuko Katafuchi (Kano Hospital). We also thank Hugh McGonigle, PhD, Jodi Smith, PhD, and Mark Cleasby, PhD from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing drafts of the manuscript.

Author information

Authors and Affiliations

  1. Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan

    Masatoshi Hara, Masanori Tokumoto & Hiroaki Ooboshi

  2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masatoshi Hara, Shigeru Tanaka, Kumiko Torisu, Yuta Matsukuma, Akihiro Tsuchimoto, Toshiaki Nakano & Takanari Kitazono

  3. Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kumiko Torisu

  4. Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Kazuhiko Tsuruya

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  1. Masatoshi Hara
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Contributions

The individual contributions of each co-author are as follows. Masatoshi Hara contributed to the study design, statistical analysis, data interpretation, and drafting of the manuscript. Shigeru Tanaka contributed to the funding, statistical analysis, data interpretation, providing intellectual content of critical importance to the work described, and drafting of the manuscript. Yuta Matsukuma, Akihiro Tsuchimoto, Kumiko Torisu, Masanori Tokumoto, and Toshiaki Nakano contributed to the data acquisition and critical revision of the manuscript. Hiroaki Ooboshi contributed to critical revision of the manuscript. Kazuhiko Tsuruya and Takanari Kitazono contributed to critical revision of the manuscript and supervision of the study. All the authors provided critical reviews of the draft and approved the final version.

Corresponding author

Correspondence to Kazuhiko Tsuruya.

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All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number UMIN000007988) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Written informed consent was obtained from all included participants included in the study.

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Hara, M., Tanaka, S., Torisu, K. et al. Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study. Clin Exp Nephrol 25, 822–834 (2021). https://doi.org/10.1007/s10157-020-02018-z

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