ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO152

Increased Cardiac Fibroblast Growth Factor 23 in Physiologic Hypertrophy Does Not Change Kidney Sodium Dependent Phosphate Transporter Expression

Session Information

  • CKD-MBD: Targets and Outcomes
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Campos, Isaac D., The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Richter, Beatrice, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Heitman, Kylie, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Yanucil, Christopher, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Thomas, Madison, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Westbrook, David Gibbs, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
  • Faul, Christian, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
Background

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone primarily produced by the bone that is elevated over the course of chronic kidney disease (CKD). In animal models of CKD, increased serum FGF23 levels cause pathologic cardiac hypertrophy via klotho-independent activation of FGF receptor 4 (FGFR4) and subsequent calcineurin/NFAT signaling in cardiomyocytes. Whether FGF23/FGFR4 also plays a role in physiologic cardiac hypertrophy, which is reversible and does not result in tissue damage, has previously been unknown. In mammals, physiologic cardiac hypertrophy is induced during pregnancy to ensure increased cardiac output. The same phenomenon is observed in intermediate feeding snakes, such as the Burmese python, where multiple organs, including the heart, undergo significant hypertrophic growth to meet the sudden increase in metabolic demands after feeding.

Methods

To investigate the role of FGFR4 signaling in physiologic cardiac hypertrophy we used virgin C57BL/6J wildtype and global FGFR4 knockout (KO) mice mated with male breeders. We investigate the effect of FGFR4 deletion on the process of adaptive cardiovascular hypertrophy at different time points during and after pregnancy. Virgin littermates served as controls. RTqPCR was used to measure gene expression.

Results

We found that mice in late pregnancy had significantly higher heart weight to tibia length ratios, regardless of the genotype. However, the area of individual cardiomyocytes was only significantly increased in wildtype mice. Serum FGF23 levels increased during pregnancy and quickly dropped after delivery and did not reduce kidney expression of NaPi 2a or 2c. We also treated neonatal rat ventricular myocytes (NRVMs) with serum from fasted and previously fed P. bivittatus in the absence and presence of an FGFR4-specific blocking antibody. We found that serum from snakes taken 12-hours and 3-days post-feeding significantly increased NRVM area, while serum from fasted snakes did not. This effect was abrogated in NRVM cultures co-treated with anti-FGFR4.

Conclusion

Our data suggests a significant role of FGFR4 in the induction of reversible physiologic cardiac hypertrophy in mice and snakes without the induced reduction of phosphate transporters in the kidney.

Funding

  • NIDDK Support