ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO190

FGF23, Erythropoietin, and Erythroferrone Levels in Autosomal Dominant Polycystic Kidney Disease Patients

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Hanudel, Mark R., UCLA, Los Angeles, California, United States
  • Salusky, Isidro B., UCLA, Los Angeles, California, United States
  • Pereira, Renata C., UCLA, Los Angeles, California, United States
  • Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Gitomer, Berenice Y., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Nowak, Kristen L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Background

Circulating FGF23 levels are higher in patients with autosomal dominant polycystic kidney disease (ADPKD) compared to patients with similar kidney function and other causes of CKD. Although bone is the major source of FGF23, erythropoietic bone marrow cells may also express FGF23 in response to erythropoietin (EPO), levels of which increase in ADPKD. We tested whether serum EPO levels in ADPKD patients are associated with circulating and bone FGF23. We also assessed serum levels of the EPO-responsive hormone erythroferrone (ERFE).

Methods

20 adult subjects with ADPKD and normal kidney function (mean ± SD eGFR 97 ± 29 ml/min/1.73m2) and 9 healthy controls participated in the study. We measured circulating C-terminal (total) FGF23 (cFGF23), intact FGF23 (iFGF23), EPO, ERFE, phosphate, calcium, PTH, 25D, 1,25D, iron, ferritin, hepcidin, and hemoglobin. Quantitative bone FGF23 levels were determined by immunohistochemical staining from bone biopsies.

Results

Circulating total FGF23 was higher in ADPKD subjects than in controls (geometric mean (95% CI) 109 (78, 153) vs. 73 (56, 95) RU/ml, p=0.050). Intact FGF23 tended to be higher (67 (57, 80) vs. 51 (39, 67) pg/ml, p=0.073). Quantitative bone FGF23 levels did not differ between the groups. Serum EPO levels were higher in ADPKD subjects (11.1 ± 6.7 vs. 6.1 ± 3.8 mIU/ml, p=0.019). Consistent with increased EPO, serum ERFE levels were also increased (17.6 ± 7.4 vs. 7.6 ± 6.2 ng/ml, p=0.001). The ADPKD subjects had higher phosphate (4.0 ± 0.5 vs. 3.6 ± 0.4 mg/dl, p=0.036) and lower 1,25D (44 (39, 49) vs. 61 (45, 82) pg/ml, p=0.039). Serum calcium, PTH, 25D, iron, ferritin, hepcidin, and hemoglobin did not differ between the groups. In the ADPKD subjects, EPO correlated with Log cFGF23 (r=0.55, p=0.021), and tended to correlate with Log iFGF23 (r=0.42, p=0.069), but not bone FGF23. After adjusting for phosphate, EPO remained associated with Log cFGF23 (β=0.58, p=0.011) and Log iFGF23 (β=0.44, p=0.053).

Conclusion

ADPKD patients with normal kidney function have increased EPO levels, which are associated with increased ERFE, and may contribute to increased circulating FGF23. EPO-induced marrow FGF23 expression has been demonstrated in rodents, and may explain the observation that EPO is associated with circulating FGF23 but not bone FGF23.