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Abstract: FR-PO161

Determinants of C-Terminal vs. Intact FGF-23 in CKD: The COMBINE Trial

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Kendrick, Cynthia A., Cleveland Clinic, Cleveland, Ohio, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago, Chicago, Illinois, United States
  • Mehta, Rupal, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
  • Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
  • Wolf, Myles, Duke University, Durham, North Carolina, United States
  • Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
Background

C-terminal FGF23 assays measures full-length and c-terminal fragments and intact assays measure full-length only. Iron deficiency and inflammation may enhance FGF23 production and cleavage and CKD may impair FGF23 cleavage. Few studies have measured both FGF23 assays concurrently in CKD. We sought to identify determinants of the FGF23 C terminal / Iintact (C/I) ratio in CKD stage 3b-4.

Methods

203 patients with eGFR 20-45 ml/min/1.73m2 participated in a randomized trial evaluating lanthanum and nicotinamide for phosphate and FGF23 lowering. FGF23 was measured using the Immutopics C-terminal and Kainos intact assays at baseline. We calculated the C/I ratio and used linear regression to identify independent determinants.

Results

Mean eGFR was 32±7 ml/min/1.72m2. Mean C-terminal FGF23 was 271±186 RU/ml and intact FGF23 was 123±92 pg/ml, which were moderately correlated (r=0.40, p<0.001). The mean C/I ratio was 2.62±2.2RU/pg. Female gender and lower calcium were independently associated with higher C/I ratio. We found no associations of eGFR, anemia, iron deficiency, or inflammation with C/I ratio.

Conclusion

Gender and calcium are differently associated with C-terminal vs. intact FGF23; associations that appear stronger than iron deficiency, anemia, inflammation, or CKD severity, in CKD stages 3b-4.

Independent Determinants of C-terminal / Intact FGF23 in Patients with eGFR 20-45 ml/min/1.73m2 who Participated in the COMBINE Trial
VariableΔ C-terminal / Intact FGF23 Ratio
(95% Confidence Interval)
Age (per year)0.01 (-0.02, 0.03)
Female1.44 (0.71, 2.16)
Non-white race-0.61 (-1.30, 0.07)
Diabetes-0.22 (-0.85, 0.41)
SBP (per mmHg higher)-0.02 (-0.03, 0.06)
eGFR (per ml/min/1.73m2 higher)0.02 (-0.03, 0.06)
ACR (per log unit higher)0.06 (-0.13, 0.24)
Calcium (per mg/dL higher)-1.05 (-1.71, -0.39)
Phosphate (per mg/dL higher)-0.16 (-0.72, 0.40)
1,25(OH)2 Vitamin D (per pg/mL higher)0.02 (-0.01, 0.04)
Ferritin (per 10 ng/mL higher)-0.00 (-0.02, 0.01)
Transferrin saturation (per % higher)-0.03 (-0.07, 0.01)
Hemoglobin (per g/dL higher)0.19 (-0.03, 0.40)
C-reactive protein (per log unit higher)-0.23 (-0.51, 0.05)
  

All variables mutually adjusted.

Funding

  • NIDDK Support