Osteoporosis International

, Volume 24, Issue 3, pp 1137–1137

Lack of predictive value of FGF23 levels on pulse wave velocity

Letter
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Dear Editor,

We thank the authors of the letter [1] for their interest in our publication and their detailed work-up of its content. We appreciate the comments and wish to briefly address the main questions raised.

In a study of 142 patients at different stages of chronic kidney disease (CKD), we reported that the plasma intact FGF23 concentration was independently associated with aortic calcification but not with pulse wave velocity (PWV) and bone mass density [2]. In comparison, Ford et al. found a correlation between intact FGF23 and PWV in a univariate analysis in a recent study of 200 CKD stage 3–4 patients—although the association was no longer statistically significant after adjustment in a multivariate analysis (as presented in Table 5 of Ford and colleagues’ article [3]). Indeed, other biomarkers (such as osteoprotegerin) were more relevant than FGF23 for PWV prediction in this latter cohort [3]. Hence, it appears to us that the two studies’ respective findings are concordant (i.e. intact FGF23 levels are not predictive of PWV in CKD patients) and that the search for optimal biomarkers for arterial stiffness must continue. We also wish to emphasize that the two studies are not straightforwardly comparable; our study included patients at different CKD stages (including advanced stages, i.e. hemodialysis), whereas the study of Ford et al. was restricted to stage 3–4 patients.

Regarding the possible instability of FGF23, we reread the cited paper with interest [4]. However, the blood samples in our study were centrifuged, separated and frozen at −80 °C immediately after collection, which was not one of the sets of conditions tested in the previous paper [4]. Hence, no definitive conclusions can be drawn in this respect and additional work is needed to test the instability hypothesis under the conditions used in our present study. It is worth noting that most of the studies (including some large cohorts) having suggested an association between FGF23 and outcomes did not use protease inhibitors [5, 6].

References

  1. 1.
    Smith ER, McMahon LP, Holt SG (2012) FGF23: instability may affect accuracy and interpretation. Osteoporosis Int. doi:10.1007/s00198-012-2036-4
  2. 2.
    Desjardins L, Liabeuf S, Renard C, Lenglet A, Lemke H-D, Choukroun G, Drueke TB, Massy ZA, European Uremic Toxin (EUTox) Work Group (2011) FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos Int 23:2017–2025. doi:10.1007/s00198-011-1838-0 PubMedCrossRefGoogle Scholar
  3. 3.
    Ford ML, Smith ER, Tomlinson LA, Chatterjee PK, Rajkumar C, Holt SG (2012) FGF-23 and osteoprotegerin are independently associated with myocardial damage in chronic kidney disease stages 3 and 4. Another link between chronic kidney disease–mineral bone disorder and the heart. Nephrol Dial Trans 27:727–733CrossRefGoogle Scholar
  4. 4.
    Smith ER, Ford ML, Tomlinson LA, Weaving G, Rocks BF, Rajkumar C, Holt SG (2011) Instability of fibroblast growth factor-23 (FGF-23): implications for clinical studies. Clin Chim Acta 412:1008–1011PubMedCrossRefGoogle Scholar
  5. 5.
    Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Jüppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCrossRefGoogle Scholar
  6. 6.
    Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu C, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  1. 1.INSERM U-1088, UFR de Médecine et Pharmacie, and Clinical Research Centre—Division of Clinical PharmacologyAmiens University Medical Center and the Jules Verne University of PicardieAmiensFrance

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