Abstract: FR-PO265

Effects of Iron Sucrose on Fibroblast Growth Factor 23 (FGF23) Levels in Iron-Deficient Patients with CKD and Heart Failure (HF)

Session Information

Category: Mineral Disease

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

Authors

  • Mehta, Rupal, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
  • Hodakowski, Alex, Northwestern University, Chicago, Illinois, United States
  • Cai, Xuan, Northwestern University, Chicago, Illinois, United States
  • Wolf, Myles S., Duke University, Durham, North Carolina, United States
  • Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
Background

Iron deficiency (ID) is a potent stimulus for increased FGF23 production. In healthy individuals with ID, upregulated FGF23 production is matched by FGF23 cleavage resulting in elevated c-terminal FGF23 (cFGF23) but normal intact FGF23 (iFGF23) levels. We hypothesize that FGF23 cleavage is impaired in CKD and HF and that the resultant imbalance between production and relatively decreased FGF23 cleavage contributes to the known elevation of iFGF23 levels in CKD and HF. Furthermore, if FGF23 cleavage is impaired in CKD and HF, we hypothesize that correction of ID in CKD and HF will lower both c- and iFGF23 levels unlike healthy individuals with normal cleavage in whom iron treatment only lowers cFGF23.

Methods

We recruited 18 individuals with ID anemia with CKD and HF to investigate the effects of 5 weekly doses of iron sucrose on c- and iFGF23 levels. ID anemia was defined as hemoglobin <12 g/dl and transferrin saturation (TSAT) <20%, or a hemoglobin <12 g/dl with a ferritin <100 mg/dl and TSAT <30%. Measurements were taken at baseline, prior to each iron dose, after 5 weeks, and 3 months later.

Results

Baseline laboratory values were as follows: mean eGFR was 36 ± 18 ml/min/1.73m2, median ferritin was 44.0 (interquartile range [IQR] 22, 44 mg/dl), median TSAT 8% (IQR 8-19), median cFGF23 335 (IQR 158-480) RU/ml, and median iFGF23 147 (IQR 81-267) pg/dl. Baseline c- and iFGF23 strongly correlated (Spearman Correlation Coefficient 0.71, p value < 0.001). After 5 weeks, median cFGF23 was 142 (IQR 90-433) RU/ml with a mean decrease of -118 Ru/ml (-135 Ru/ml). Median iFGF23 was 125 (IQR 97-224) pg/dl, with a mean a decrease of 13 (± 70) pg/dl. No significant changes in eGFR or phosphate were appreciated.

Conclusion

ID patients with CKD and HF have elevated levels of c- and iFGF23. Treatment with iron sucrose lowers cFGF23 and may lower iFGF23 in states where FGF23 cleavage is impaired such as CKD and HF.

Funding

  • Private Foundation Support