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Review
. 2022 Aug;33(8):1448-1458.
doi: 10.1681/ASN.2022010036. Epub 2022 Apr 8.

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

Candice Z Ulmer  1 , Kittrawee Kritmetapak  2 , Ravinder J Singh  3   4 , Hubert W Vesper  1 , Rajiv Kumar  5   6
Affiliations
Review

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

Candice Z Ulmer et al. J Am Soc Nephrol. 2022 Aug.

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.

Keywords: mass spectrometry; mineral metabolism; parathyroid hormone.

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Figures

Figure 1.
Figure 1.
Long-standing CKD and ESKD are associated with metabolic disturbances that lead to hypersecretion of PTH and FGF23, hyperphosphatemia, calcitriol deficiency and resistance, and hypocalcemia. Common complications of secondary hyperparathyroidism include bone diseases and cardiovascular calcifications that may contribute to cardiovascular mortality. CaSR, calcium-sensing receptor; EPO, erythropoietin; FGF23, fibroblast growth factor 23; FGFR1, fibroblast growth factor receptor 1; RAAS, renin-angiotensin-aldosterone system; VDR, vitamin D receptor.
Figure 2.
Figure 2.
Serum concentrations of PTH 1–84 and PTH fragments increased as kidney function declined, and increased significantly when the eGFR decreased to ≤17–23 ml/min per 1.73 m2. Reprinted from ref. , with permission.
See this image and copyright information in PMC

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