The published observational data show similarly sized epidemiologic associations between increased fibroblast growth factor-23 (FGF-23) concentration and risk of a range of cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes. There is also an absence of any clear exposure-response relationship.1
Pelletier and Fouque2 have hypothesized that Klotho modifies FGF-23 associations with cardiovascular outcomes, and confirmation in large-scale studies is of interest. Such analyses, however, are unlikely to provide an explanation for the nonspecificity of FGF-23 associations. Instead, as recommended by Zhou et al.,3 further mechanistic experiments are needed. We suggest that such studies include the full range of noncardiovascular outcomes identified as associated with FGF-23. In the absence of good mechanistic evidence clearly supporting FGF-23’s role in a much wider range of disease processes, residual confounding is currently the most plausible explanation for the nonspecific associations. The epidemiology is suggesting the relationship between FGF-23 and cardiovascular disease risk may not be one of cause and effect.
Disclosures
None.
Acknowledgments
W.G.H. is supported by a Medical Research Council and Kidney Research UK Professor David Kerr Clinician Scientist Award.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
See related Letters to the Editor, “Fibroblast Growth Factor-23 Is Not a Single Bystander in Chronic Kidney Disease Mortality,” and “Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney Disease” on pages 2601 and 2602, respectively.
- Copyright © 2018 by the American Society of Nephrology