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Circulating fibroblast growth factor 21 links hemodynamics with kidney function in middle-aged and older adults: A mediation analysis

Hypertension Research volume 45, pages 125–134 (2022)Cite this article

Abstract

Altered hemodynamics are commonly observed in individuals with declining renal function; however, the pathophysiological mechanisms linking renal dysfunction and hemodynamics have not been fully elucidated. Fibroblast growth factor 21 (FGF21), which upregulates sympathetic nerve activity, can alter systemic hemodynamics, and its level can increase as renal function declines. This study aimed to determine the associations among circulating FGF21 levels, hemodynamics, and renal function in middle-aged and older adults. In a total of 272 middle-aged and older adults (age range: 46–83 years), estimated glomerular filtration rate (eGFR), hemodynamics (brachial and aortic blood pressure and aortic pulse wave velocity [PWV]), and serum FGF21 levels were measured. For mediation analysis, hemodynamic parameters were entered as outcomes. eGFR or log-transformed urinary albumin and creatinine ratio (UACR) and log-transformed serum FGF21 levels were set as the predictors and mediator, respectively. According to multivariable regression models after adjusting for potential covariates, serum FGF21 levels were significantly associated with brachial systolic blood pressure (β = 0.140), pulse pressure (β = 0.136), and aortic PWV (β = 0.144). Mediation analyses showed that serum FGF21 levels significantly mediated the relationship of eGFR with brachial systolic blood pressure (indirect effect [95% confidence interval]: −0.032 [−0.071, −0.002]), pulse pressure (−0.019 [−0.041, −0.001]), and aortic PWV (−0.457 [−1.053, −0.021]) and the relationship of UACR with aortic PWV (7.600 [0.011, 21.148]). These findings suggest that elevated circulating FGF21 levels partially mediate the association of elevated blood pressure and/or aortic stiffness with renal dysfunction in middle-aged and older adults.

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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

We thank the research members of SM’s laboratory and Michiru Hotta (University of Tsukuba) for their assistance in collecting the data.

Funding

This work was supported in part by the KAKENHI Grant of Japan Society for the Promotion of Science (19H03995), a Grant-in-Aid for Research Fellowships of Japan Society for the Promotion of Science for Young Scientists (20J20892), and a grant from the advanced research initiative for human high performance (ARIHHP), University of Tsukuba.

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Authors and Affiliations

  1. Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

    Masahiro Matsui

  2. Japan Society for the Promotion of Science, Tokyo, Japan

    Masahiro Matsui

  3. Faculty of Health and Sport Sciences, University of Tsukuba, Ibaraki, Japan

    Keisei Kosaki & Seiji Maeda

  4. Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan

    Makoto Kuro-o

  5. Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

    Chie Saito & Kunihiro Yamagata

  6. R&D Center for Smart Wellness City Policies, University of Tsukuba, Ibaraki, Japan

    Kunihiro Yamagata

  7. Faculty of Sport Sciences, Waseda University, Saitama, Japan

    Seiji Maeda

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MM: investigation, formal analysis, and writing—original draft. KK: conceptualization, investigation. MK: writing—review and editing. CS: writing—review and editing. KY: writing—review and editing. SM: funding acquisition, project administration, supervision, and writing—review and editing

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Correspondence to Seiji Maeda.

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Matsui, M., Kosaki, K., Kuro-o, M. et al. Circulating fibroblast growth factor 21 links hemodynamics with kidney function in middle-aged and older adults: A mediation analysis. Hypertens Res 45, 125–134 (2022). https://doi.org/10.1038/s41440-021-00782-3

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