Abstract: FR-PO259

Erythropoietin Is a Major Determinant of C-Terminal Fibroblast Growth Factor 23

Session Information

Category: Mineral Disease

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

Authors

  • Eisenga, Michele F., University Medical Center Groningen, Groningen, Netherlands
  • De Borst, Martin H., University Medical Center Groningen, Groningen, Netherlands
  • de Jong, Maarten A., University Medical Center Groningen, Groningen, Netherlands
  • Bakker, Stephan J.L., University Medical Center Groningen, Groningen, Netherlands
  • Gaillard, Carlo A., University Medical Center Groningen, Groningen, Netherlands
Background

An increased plasma level of the phosphaturic hormone fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality and allograft loss in renal transplant recipients (RTR). Similarly, high erythropoietin (EPO) levels increase the risk of adverse outcomes in RTR. Here, we investigated whether EPO modulates C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in RTR and chronic kidney disease (CKD) patients.

Methods

Plasma cFGF23 and iFGF23 were measured with ELISA in two single-center RTR cohorts. Serum EPO levels were measured on Immulite 2000 assay. Statistical analyses were performed using univariable linear regression followed by stepwise backward linear regression. Additionally, we assessed the effect of exogenous EPO on FGF23 in a post-hoc analysis of a randomized trial in CKD patients who received exogenous EPO (50 IU/kg/wk) for 52 weeks (EPOCARES, Eur J Heart Fail 2010;12:943-50) using linear mixed models.

Results

We included 680 stable RTR (age 53±13 years; 56% males at 5.4 (1.9-12.1 years after Tx). Median [IQR] cFGF23 was 140 (95-234) RU/ml, median iFGF23 was 61 (43-100) pg/mL, EPO was 6.9 (4.2-11.2) IU/L, and mean eGFR was 47±16 ml/min/1.73m2. In univariable analysis, EPO was a major determinant of cFGF23 (ß=0.24, P<0.001), but not of iFGF23 (ß=0.04, P=0.35). Upon multivariable analysis, EPO remained a major determinant of cFGF23 (ß=0.20, P<0.001), independent of known determinants including phosphate (ß=0.19, P<0.001), hemoglobin (ß=-0.13, P<0.001), and eGFR (ß =-0.35, P<0.001). In an independent replication cohort of 598 RTR, EPO was also a major determinant of cFGF23, independent of potential confounders (ß=0.22, P<0.001). Finally, in 56 CKD patients, exogenous EPO was significantly associated with an increase in cFGF23 (P=0.04), but not iFGF23 (P=0.21).

Conclusion

Serum EPO levels are a major, potentially modifiable independent determinant of serum cFGF23 in RTR, independently of known correlates including eGFR and phosphate. In CKD patients, exogenous EPO increased cFGF23 levels. We found no relationship between EPO and iFGF23 in either analysis. Our data suggest that EPO resistance, or an underlying mechanism, is related to FGF23 processing in CKD and after kidney transplantation.