» Articles » PMID: 39829956

Unlocking the Mysteries of N-oxPTH: Implications for CKD Patients

Overview
Date 2025 Jan 20
PMID 39829956
Authors
Affiliations
Soon will be listed here.
Abstract

Parathyroid hormone (PTH) is a pivotal hormone that regulates serum calcium and phosphate and is closely associated with higher risk of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). PTH can undergo oxidation at methionine 8 and methionine 18 of the molecule. This oxidation process leads to a lower binding affinity to the PTH receptor due to molecular refolding, particularly for PTH oxidized at methionine 8. Although, the oxidation of PTH has been reported for several decades, it is only recently that a method has been developed to detect non-oxidized PTH (n-oxPTH) levels. The utilization of this assay enables the precise detection of n-oxPTH levels and facilitates the evaluation of their correlation with poor prognosis in patients with CKD. However, the current available clinical research findings indicate that n-oxPTH does not demonstrate clinical superiority over iPTH. Here, we provide a comprehensive review on the mechanism of PTH oxidation, the n-oxPTH assay method, and its correlation with iPTH and clinical outcomes.

References
1.
Kritmetapak K, Losbanos L, Hines J, OGrady K, Ulmer C, Vesper H . Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure. Clin Chem. 2021; 67(6):843-853. PMC: 8167341. DOI: 10.1093/clinchem/hvab013. View

2.
Chu L, Forte L, Anast C, Cohn D . Interaction of parathyroid hormone with membranes of kidney cortex: degradation of the hormone and activation of adenylate cyclase. Endocrinology. 1975; 97(4):1014-23. DOI: 10.1210/endo-97-4-1014. View

3.
Lu Y, Zeng S, Chu C, Hasan A, Slowinski T, Yin L . Non-oxidized PTH (n-oxPTH) is associated with graft loss in kidney transplant recipients. Clin Chim Acta. 2020; 508:92-97. DOI: 10.1016/j.cca.2020.05.022. View

4.
Russell J, Lettieri D, Sherwood L . Suppression by 1,25(OH)2D3 of transcription of the pre-proparathyroid hormone gene. Endocrinology. 1986; 119(6):2864-6. DOI: 10.1210/endo-119-6-2864. View

5.
ORIORDAN J, Woodhead J, Hendy G, Parsons J, Robinson C, Keutmann H . Effect of oxidation on biological and immunological activity of porcine parathyroid hormone. J Endocrinol. 1974; 63(1):117-24. DOI: 10.1677/joe.0.0630117. View