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Fibroblast growth factor 23 and renal function among young and healthy individuals

  • Raffaele Bernasconi ORCID logo , Stefanie Aeschbacher , Steffen Blum , Michel Mongiat , Marc Girod , John Todd , Joel Estis , Niamh Nolan , Harald Renz , Lorenz Risch , David Conen and Martin Risch EMAIL logo
Published/Copyright: May 1, 2018

Abstract

Background:

Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals.

Methods:

Healthy individuals aged 25–41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion.

Results:

The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR – CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase −3.81; 95% CI [−5.42; −2.20]; p<0.0001). Furthermore, we found a linear association between FGF-23 and endothelin-1 (β per 1 log-unit increase 0.06; [0.01, 0.11]; p=0.01). In addition, we established a significant relationship of FGF-23 with fractional phosphate excretion (β per 1 log-unit increase 0.62; [0.08, 1.16]; p=0.03).

Conclusions:

Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.


Corresponding authors: Martin Risch, MD, Labormedizinisches Zentrum Dr. Risch, Vaduz, Principality of Liechtenstein

Acknowledgments

We thank the staff and participants of the GAPP study for their important contributions.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The Swiss National Science Foundation (Funder Id: 10.13039/501100001711), the Liechtenstein Government, the Swiss Heart Foundation (Funder Id: 10.13039/501100004362), the Swiss Society of Hypertension, the University of Basel (Funder Id: 10.13039/100008375), the University Hospital Basel, the Mach-Gaensslen Foundation, the Hanela Foundation, Schiller AG and Novartis (Funder Id: 10.13039/100004336) supported the GAPP study. Endothelin-1 was measured free of charge by Singulex, Inc., Alameda, CA 94502, USA. Reagents for FGF-23 measurements were provided at a reduced cost by Diasorin Switzerland AG, Rotkreuz, Switzerland.

  3. Employment or leadership: John Todd, Joel Estis and Niamh Nolan are employees of Singulex, Inc.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-1183).


Received: 2017-12-19
Accepted: 2018-03-08
Published Online: 2018-05-01
Published in Print: 2018-08-28

©2018 Walter de Gruyter GmbH, Berlin/Boston

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