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High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity

Candice Z. Ulmer, Kittrawee Kritmetapak, Ravinder J. Singh, Hubert W. Vesper and Rajiv Kumar
JASN May 2022, ASN.2022010036; DOI: https://doi.org/10.1681/ASN.2022010036
Candice Z. Ulmer
1Clinical Chemistry Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Kittrawee Kritmetapak
2Division of Nephrology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Ravinder J. Singh
3Immunochemical Core Laboratory, Mayo Clinic, Rochester, Minnesota
4Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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Hubert W. Vesper
1Clinical Chemistry Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Rajiv Kumar
5Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
6Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
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Abstract

Full-length parathyroid hormone (PTH 1–84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1–84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1–84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1–84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1–84, PTH fragments, and post-translationally modified PTH 1–84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.

  • parathyroid hormone
  • mineral metabolism
  • mass spectrometry
  • Copyright © 2022 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 33 (6)
Journal of the American Society of Nephrology
Vol. 33, Issue 6
June 2022
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High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity
Candice Z. Ulmer, Kittrawee Kritmetapak, Ravinder J. Singh, Hubert W. Vesper, Rajiv Kumar
JASN May 2022, ASN.2022010036; DOI: 10.1681/ASN.2022010036

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High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity
Candice Z. Ulmer, Kittrawee Kritmetapak, Ravinder J. Singh, Hubert W. Vesper, Rajiv Kumar
JASN May 2022, ASN.2022010036; DOI: 10.1681/ASN.2022010036
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  • Article
    • Abstract
    • Biosynthesis and Bioactivity of Full-Length PTH and PTH Fragments
    • Altered Metabolism of PTH in CKD
    • The Chemical Identity and Concentrations of Circulating PTH Fragments Was Unknown until Recently
    • Identification of Novel PTH Fragments in the Serum of Subjects with and without CKD/ESKD
    • Bioactivity of Amino-Terminally Truncated PTH Fragments Reveals Unique Properties in Cultured Cells
    • Use of LC-HRMS to Confirm the Existence of Post-Translationally Modified PTH 1–84; Quantitation of Oxidized PTH 1–84
    • Current Methodologies for PTH Measurement
    • PTH Standardization: A Major Problem in Laboratory Medicine
    • Unique Advantages and Limitations of Mass Spectrometry in Resolving PTH Measurement Issues
    • Clinical Relevance of Measuring PTH Fragments
    • Integration of PTH LC-HRMS Assays with Bone Histomorphometry
    • Disclosures
    • Funding
    • Acknowledgments
    • Author Contributions
    • Footnotes
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More in this TOC Section

  • Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United States
  • Tissue Culture Models of AKI: From Tubule Cells to Human Kidney Organoids
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Keywords

  • parathyroid hormone
  • mineral metabolism
  • mass spectrometry

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