Preclinical data suggest that hypoxia stimulates fibroblast growth factor 23 (FGF23) transcription and cleavage in osteocytes, resulting in elevated circulating c-terminal (cFGF23) levels but normal intact FGF23 (iFGF23) levels. We conducted a case-control study within the Hispanic Community Health Study/Study of Latinos to investigate whether sleep disordered breathing, as a model of hypoxemia, is independently associated with elevated cFGF23 levels in the general population and with elevated cFGF23 and iFGF23 levels in patients with chronic kidney disease (CKD), in whom FGF23 cleavage may be impaired. Cases (n = 602) had severe sleep disordered breathing defined as an apnea/hypopnea index (AHI) of ≥30. Controls without severe sleep disordered breathing (n = 602) were matched for sex and CKD stage. The median AHI in the cases was 45.8 (IQR 35.5–62.5) compared to 2.6 (IQR 0.6–8.2) in the controls. Cases had higher cFGF23 levels than controls (66.2 RU/mL, IQR 52.8–98.4 vs. 61.2 RU/mL, IQR 49.5–80.1, p value <0.001). There were no differences in iFGF23 levels between cases and controls. In adjusted linear regression and multinomial regression analyses, body mass index attenuated the relationship between severe sleep disordered breathing and cFGF23 levels. No significant relationships were seen in analyses of severe sleep disordered breathing and iFGF23 levels or in analyses of iFGF23 and cFGF23 stratified by CKD status. Additional studies using other models of intermittent and chronic hypoxia are needed to confirm whether hypoxia stimulates FGF23 transcription in humans and to determine the impact on iFGF23 levels in CKD.
Bibliographical noteFunding Information:
All authors have read the journal's policy on disclosure of potential conflicts of interest. RM has interest in Abbot Laboratories, AbbVie, Inc. and Teva Pharmaceuticals Industries Ltd. TI has received honoraria from Bayer and grant support from Shire. MW has received research support, honoraria or consultant fees from Amgen, Ardelyx, DiaSorin, Keryx, Lilly, Pfizer, Shire and Ultragenyx.
Investigators website - http://www.cscc.unc.edu/hchs/ . This study was supported by grants R01DK081374 (MW), K24DK093723 (MW), R01DK102438 (TI), National Kidney Foundation of Illinois Young Investigator Grant (RM), and a Strategically Focused Research Network Center Grant from the American Heart Association (MW). The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements.
- Chronic kidney disease
- Fibroblast growth factor 23
- Sleep disordered breathing