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Abstract: PO0353

Chemical Characterization and Quantitation of Circulating Intact Parathyroid Hormone and Parathyroid Hormone Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Kritmetapak, Kittrawee, Khon Kaen University, Khon Kaen, Thailand
  • Losbanos, Louis A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hines, Jolaine M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • O'Grady, Katherine, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ulmer, Candice Z., Centers for Disease Control and Prevention, Atlanta, Georgia, United States
  • Vesper, Hubert W., Centers for Disease Control and Prevention, Atlanta, Georgia, United States
  • Enders, Felicity T., 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

The precise concentrations of full-length parathyroid hormone (PTH 1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure (CRF) are unknown.

Methods

We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantitate PTH 1-84 and PTH fragments in the serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, full-length PTH and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay.

Results

Full-length PTH 1-84 and eight PTH fragments (PTH 28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when the eGFR declined to less than 17-23 mL/min/1.73 m2. Serum concentrations of PTH 1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. Serum PTH 1-84 concentrations measured by LC-HRMS were significantly lower compared with PTH measured by an iPTH immunoassay in patients with eGFRs of less than 30 mL/min/1.73 m2. PTH 7-84 was below the lower limit of quantitation of the method (<50 pg/mL).

Conclusion

LC-HRMS accurately quantitates full-length PTH, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in the serum of patients with progressive renal failure. Serum concentrations of PTH 1-84 and PTH fragments increase when eGFR decreases to less than 17-23 mL/min/1.73 m2. PTH values measured by LC-HRMS are lower than those obtained from an iPTH immunoassay in severe CRF

Funding

  • Other NIH Support