Abstract: FR-PO260

Acute Blood Loss Stimulates Fibroblast Growth Factor 23 Production

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Rabadi, Seham M., New York Medical College, Valhalla, New York, United States
  • Udo, Ikemesit, New York Medical College, Valhalla, New York, United States
  • Leaf, David E., Harvard Medical School, Boston, Massachusetts, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Christov, Marta, New York Medical College, Valhalla, New York, United States
Background

Fibroblast growth factor 23 (FGF23) production is upregulated by iron deficiency and hypoxia. The influence of acute blood loss and erythropoietin on FGF23 production is unknown.

Methods

Using wild-type C57BL/6 mice we determined the effect of acute loss of 10% total blood volume on Fgf23 mRNA expression in bone and circulating total FGF23 protein levels (measured by the c-terminal assay, cFGF23) and other markers of mineral metabolism. We also measured plasma cFGF23 levels in 131 critically ill patients admitted to the intensive care unit to assess the association with number of blood transfusions as an indicator of acute blood loss.

Results

We found that acute blood loss leads to an increase in plasma cFGF23 levels 3-5 fold within six hours, while plasma levels of intact FGF23, phosphate, calcium, parathyroid hormone, iron, and ferritin remain similar to control mice without acute blood loss. Volume resuscitation with PBS did not significantly alter these findings. The increase in plasma cFGF23 levels in bled animals was accompanied by increased plasma erythropoietin levels at 6 hours. Administration of erythropoietin led to an acute increase in plasma cFGF23 levels similar to that observed in acute blood loss. Fgf23 mRNA expression was increased 20-fold in bone marrow, but not in bone, of bled versus control mice, suggesting bone marrow as a key source of elevated plasma FGF23 levels following acute blood loss. To extend these findings to humans, we measured plasma cFGF23 levels in 131 critically ill patients. In univariate and multivariate models, we found a positive association between number of red blood cell transfusions, an indirect indicator of acute blood loss, and plasma cFGF23 levels.

Conclusion

We conclude that FGF23 production is rapidly increased after acute blood loss, and that erythropoietin may be the mediator of this increase. Thus, erythropoietin may represent a novel physiologic regulator of FGF23 production.

Funding

  • NIDDK Support