RESUMEN

Parathyroid hormone (PTH) is the key hormone regulating calcium homeostasis and, as such, is an important diagnostic and prognostic marker. Although the measurement of PTH has greatly improved over the past few decades, oxidation status thereof is unaccounted for in currently used assays. PTH can be oxidized on methionine residues located at amino acid positions 8 and 18. This is a relevant post-translational modification as, due to refolding of the molecule, it results in the decreased ability to activate the PTH1 receptor. Although this loss of activity after oxidation was observed as early as 1934, only recently a method was developed to measure and distinguish non-oxidized PTH (n-oxPTH) from oxidized PTH. This method creates exciting possibilities for studying more specifically the role of n-oxPTH in physiology and pathology. Therefore, it can now be explored what the clinical implications of measuring n-oxPTH will be. Herein, we review the available evidence of the effect of oxidation on the biological activity of PTH. We also discuss studies examining the mechanism of PTH oxidation in vivo and efforts to stabilize synthetic PTH ex vivo for therapeutic applications. Lastly, the available studies regarding the clinical significance of n-oxPTH are evaluated and future directions discussed.

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RESUMEN

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) leading high mortality and even long-term morbidity. SHPT is manifested by elevation of parathyroid hormone (PTH) and accurate determining the level of serum PTH is very essential for early diagnosis of SHPT secondary to CKD. It is very important to match the values obtained for intact parathormone (iPTH) and 1- 84 PTH with the minimized measurement bias. OBJECTIVES: The present study aimed to first determine the agreement value between the iPTH and 1- 84 PTH measures in patients with hyperparathyroidism secondary to endstage renal disease under chronic hemodialysis. Then, we attempted to determine the best cutoff values for these two measurements for detecting SHPT in such patients. PATIENTS AND METHODS: This cross-sectional study was conducted on hemodialysis patients. The value of study biomarkers including iPTH and 1- 84 PTH was assessed. RESULTS: A strong positive association was revealed between the two indicators of iPTH and 1-84 PTH (r = 0.800, P < 0.001). The linear association between these two parameters is independent to baseline characteristics including gender, age, body mass index, and medical history. Among all biochemical elements, the value of 1-84 PTH was only associated with serum calcium level negatively (r = -0.267, P = 0.027) and alkaline phosphatase positively (r = 0.359, P = 0.003). Considering iPTH as the reference and according to the area under the ROC curve (AUC), 1-84 PTH had high value to predict hyperparathyroidism (AUC = 0.926, P < 0.001). The best cutoff point for 1-84 PTH to discriminate hyperparathyroidism from normal condition was 60 yielding a sensitivity of 92.3% and a specificity of 79.1%. Among other baseline laboratory parameters, only alkaline phosphatase had an acceptable value for diagnosing hyperparathyroidism (AUC = 0.731, P = 0.001). CONCLUSIONS: The measurement of both iPTH and 1-84 PTH is valuable for predicting hyperparathyroidism secondary to CKD, but according to lower cost and comparableeffectiveness of iPTH measurement, this assay may be comparable to 1-84 PTH to predict this consequence.