Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.
Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.
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DOI：
10.1093/clinchem/hvab013
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发表时间：
2021-06-01
影响因子：
9.3
通讯作者：
Kumar R
中科院分区：
文献类型：
--
作者：
Kritmetapak K;Losbanos LA;Hines JM;O'Grady KL;Ulmer CZ;Vesper HW;Enders FT;Singh RJ;Kumar R
全长甲状旁腺激素（PTH 1 -84）的精确浓度和PTH片段的身份和浓度在不同阶段的慢性肾功能衰竭患者是未知的。我们开发了一种液相色谱-高分辨质谱（LC-HRMS）方法来表征和定量221例进行性肾功能不全患者血清中的PTH 1 -84和PTH片段。通过基质结合的氨基末端或羧基末端区域特异性抗体捕获并从基质洗脱后，使用LC-HRMS鉴定并定量PTH 1 -84和PTH片段。使用完整PTH（iPTH）免疫测定法同时测量PTH。明确鉴定了全长PTH 1 -84和8个PTH片段（PTH 28 -84、34-77、34-84、37-77、37-84、38-77、38-84和45-84），并显示当eGFR降至≤17-23 mL/min/1.73 m2时显著增加。当通过氨基末端或羧基末端免疫捕获方法捕获后通过LC-HRMS测量时，PTH 1 -84的血清浓度相似。在eGFR <30 mL/min/1.73 m2的患者中，使用LC-HRMS测量的血清PTH浓度显著低于使用iPTH免疫测定法测量的PTH。PTH 7 -84和氧化形式的PTH 1 -84低于检测限（分别为30和50 pg/mL）。LC-HRMS鉴定进行性肾衰竭患者循环PTH 1 -84、羧基末端PTH片段和中段PTH片段。当eGFR降至≤17-23 mL/min/1.73 m2时，血清PTH 1 -84及其片段显著升高。使用LC-HRMS测量的PTH浓度往往低于使用iPTH免疫测定法测量的PTH浓度，特别是在重度慢性肾衰竭中。我们的数据不支持循环PTH 7 -84和氧化PTH 1 -84的存在。
The precise concentrations of full-length parathyroid hormone (PTH1–84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1–84 and PTH fragments in 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, PTH1–84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. Full-length PTH1–84 and 8 PTH fragments (PTH28–84, 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 an eGFR declined to ≤17–23 mL/min/1.73m2. Serum concentrations of PTH1–84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7–84 and oxidized forms of PTH1–84 were below the limit of detection (30 and 50 pg/mL, respectively). LC-HRMS identifies circulating PTH1–84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1–84 and its fragments markedly rise when an eGFR decreases to ≤17–23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7–84 and oxidized PTH1–84.
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影响因子：
15.9
作者：
MARTIN, KJ;HRUSKA, KA;SLATOPOLSKY, E
通讯作者：
SLATOPOLSKY, E
影响因子：
--
作者：
DAMOUR, P;HUET, PM;ROSENBLATT, M
通讯作者：
ROSENBLATT, M
影响因子：
2.2
作者：
Michelangeli, VP;Heyma, P;Ebeling, PR
通讯作者：
Ebeling, PR
影响因子：
4
作者：
BRINGHURST, FR;STERN, AM;POTTS, JT
通讯作者：
POTTS, JT
影响因子：
5.8
作者：
D'Amour, P;Räkel, A;Cantor, T
通讯作者：
Cantor, T