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Abstract: PO0368

Hyperphosphatemia with Elevated Serum FGF-23 and PTH, Reduced Calcitriol, and Normal FGF7 Concentrations Characterizes Chronic Renal Failure in Humans

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Kritmetapak, Kittrawee, Mayo Clinic Minnesota, Rochester, United States
  • Losbanos, Louis A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Berent, Taylor, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ashrafzadeh-Kian, Susan L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Algeciras-Schimnich, Alicia, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hines, Jolaine M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Singh, Ravinder, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Kumar, Rajiv, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Fibroblast growth factor 23 (FGF23), a phosphatonin produced by osteocytes, regulates phosphate (Pi) homeostasis and is increased in CKD. A recent study showed that low serum (s) concentrations of FGF7 may contribute to hyperphosphatemia in patients with hypophosphatasia, and are elevated in some patients with tumor-induced osteomalacia and hypophosphatemia. We hypothesized that FGF7 might play a role in compensating for elevated Pi concentrations in CKD.

Methods

We measured serum concentrations of intact FGF7 (iFGF7, R&D Systems), iFGF23 (Eagle Biosciences), intact parathyroid hormone (iPTH) by enzyme-linked immunosorbent assays and determined s Pi, and 1,25-dihydroxyvitamin D (1,25(OH)2D, by mass spectrometry) among 75 non-kidney transplant patients with varying estimated glomerular filtration rate (eGFR). Relationships between these parameters and eGFR were explored.

Results

For eGFR of 60 or more (n=29), 45-59 (n=14), 30-44 (n=9), 15-29 (n=13), and under 15 mL/min/1.73 m2 (n=10), the median (IQ25-75) iFGF23 concentrations were 41.9 (33.1-47.4), 56.4 (47.4-58.6), 62.9 (53.2-75.6), 117.5 (87.6-137.2), and 327.5 (195.1-456.3) pg/mL, respectively (P <0.01). At comparable eGFRs, median (IQ25-75) iFGF7 concentrations were 46.1 (40.8-56.1), 43.1 (39.2-49.2), 45.4 (38.5-53.8), 47.7 (38.5-54.6), and 46.1 (40.8-54.6) pg/mL, respectively (P = 0.81). Negative correlations between Pi (r = –0.46; P <0.01), iPTH and eGFR (r = –0.33; P <0.05), and a positive correlation between 1,25(OH)2D and eGFR (r = 0.51; P <0.01) were demonstrated. Significant increases in iFGF23, iPTH, and Pi were observed at eGFRs of less than 33 (95% CI, 26.40-40.05), 29 (95% CI, 22.51-35.36) and 22 mL/min/1.73m2 (95% CI, 19.25-25.51), respectively. Moreover, significant decreases in 1,25(OH)2D were observed at eGFRs of less than 59 mL/min/1.73m2 (95% CI, 36.57-81.43). iFGF7 concentrations did not significantly correlate with eGFR, Pi, iFGF23, iPTH, and 1,25(OH)2D.

Conclusion

Increases in serum concentrations of Pi, iFGF23, iPTH, but not iFGF7, and decreases in 1,25(OH)2D are observed as renal function declines in CKD.

Funding

  • Other NIH Support