Effects of Parathyroidectomy on Plasma iPTH and (1–84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease

Chen Huimin; Cui Ying; Xing Changying; Zha Xiaoming; Zhang Yan; Wang Qingting; Ma Haoyang; Zhang Lina; Zeng Ming; Yang Guang; Lv Xiaolin; Yogendranath Purrunsing; Wang Ningning

doi:10.1055/a-0723-2807

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(10): 761-767
DOI: 10.1055/a-0723-2807

Endocrine Care

Effects of Parathyroidectomy on Plasma iPTH and (1–84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease

Chen Huimin

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Cui Ying

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Xing Changying

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Zha Xiaoming

²Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Zhang Yan

³Department of Laboratory Medcine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Wang Qingting

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Ma Haoyang

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Zhang Lina

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Zeng Ming

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Yang Guang

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Lv Xiaolin

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Yogendranath Purrunsing

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

,

Wang Ningning

¹Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

› Author Affiliations

Abstract

Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1–84)PTH and (7–84)PTH fragments, which have antagonistic effects on (1–84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1–84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1–84)PTH levels, respectively. Circulating (7–84)PTH levels were calculated by subtracting the (1–84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1–84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1–84)PTH and (7–84)PTH concentrations increased as iPTH levels increased, and (7–84)PTH increased more evidently. Plasma iPTH, (1–84)PTH and (7–84)PTH levels were 1530.5 (885.0–2111.5) pg/ml, 683.1 (431.4–1018.0) pg/ml, and 739.3 (452.6–1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1–84)PTH and (7–84)PTH concentrations decreased considerably, and the (1–84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1–84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.

Key words

chronic kidney disease-mineral and bone disorder - secondary hyperparathyroidism - intact parathyroid hormone - (1–84) parathyroid hormone - parathyroidectomy

Full Text

References

References
1 Hedgeman E, Lipworth L, Lowe K, Saran R, Do T, Fryzek J. International burden of chronic kidney disease and secondary hyperparathyroidism: A systematic review of the literature and available data. Int J Nephrol 2015; 184321
2 Zhang J, Yu X, Sun B, Bai J, Wei Y, Zha X, Cui Y, Zeng M, Zhang J, Liu J, Mao H, Zhang B, Ren H, Ge Y, Xu X, Shen Z, Xing C, Cao K, Wang N. Parathyroidectomy and heart rate variability in patients with stage 5 CKD. Clin J Am Soc Nephrol 2013; 8: 1378-1387
3 Hernandes FR, Canziani ME, Barreto FC, Santos RO, Moreira VM, Rochitte CE, Carvalho AB. The shift from high to low turnover bone disease after parathyroidectomy is associated with the progression of vascular calcification in hemodialysis patients: A 12-month follow-up study. PloS One 2017; 12: e0174811
4 Cavalier E, Plebani M, Delanaye P, Souberbielle JC. Considerations in parathyroid hormone testing. Clin Chem Lab Med 2015; 53: 1913-1919
5 Silverman R, Yalow RS. Heterogeneity of parathyroid hormone. Clinical and physiologic implications. J Clin Invest 1973; 52: 1958-1971
6 Daugaard H, Egfjord M, Olgaard K. Influence of calcium on the metabolism of intact parathyroid hormone by isolated perfused rat kidney and liver. Endocrinology 1990; 126: 1813-1820
7 Bringhurst FR, Stern AM, Yotts M, Mizrahi N, Segre GV, Potts Jr JT. Peripheral metabolism of PTH: Fate of biologically active amino terminus in vivo. Am J Physiol 1988; 255: E886-E893
8 Nakajima K, Nohtomi K, Sato M, Takano K, Sato K. PTH(7-84) inhibits PTH(1-34)-induced 1,25-(OH)2D3 production in murine renal tubules. Biochem Biophys Res Commun 2009; 381: 283-287
9 Nguyen-Yamamoto L, Rousseau L, Brossard JH, Lepage R, D'Amour P. Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor. Endocrinology 2001; 142: 1386-1392
10 Malluche HH, Koszewski N, Monier-Faugere MC, Williams JP, Mawad H. Influence of the parathyroid glands on bone metabolism. Eur J Clin Invest 2006; 36 (Suppl. 02) 23-33
11 Souberbielle JC, Brazier F, Piketty ML, Cormier C, Minisola S, Cavalier E. How the reference values for serum parathyroid hormone concentration are (or should be) established?. J Endocrinol Invest 2017; 40: 241-256
12 Tanaka H, Komaba H, Koizumi M, Kakuta T, Fukagawa M. Novel electrochemiluminescence immunoassay exclusively for full-length parathyroid hormone during treatment with cinacalcet for secondary hyperparathyroidism. Therap Apheresis Dial 2011; 15 (Suppl. 01) 56-61
13 Yamashita H, Gao P, Cantor T, Noguchi S, Uchino S, Watanabe S, Ogawa T, Kawamoto H, Fukagawa M. Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism. Surgery 2004; 135: 149-156
14 Monier-Faugere MC, Geng Z, Mawad H, Friedler RM, Gao P, Cantor TL, Malluche HH. Improved assessment of bone turnover by the PTH-(1-84)/large C-PTH fragments ratio in ESRD patients. Kidney Int 2001; 60: 1460-1468
15 Inaba M, Okuno S, Imanishi Y, Ishimura E, Yamakawa T, Shoji S. Increased active PTH(1-84) fraction as a predictor of poor mortality in male hemodialysis patients. Osteop Inter 2013; 24: 2863-2870
16 Li J, Xiao Z, Hu X, Li Y, Zhang X, Zhang S, Shan A. Total parathyroidectomy with forearm auto-transplantation improves the quality of life and reduces the recurrence of secondary hyperparathyroidism in chronic kidney disease patients. Medicine (Baltimore) 2017; 96: e9050
17 Isakova T, Nickolas TL, Denburg M, Yarlagadda S, Weiner DE, Gutierrez OM, Bansal V, Rosas SE, Nigwekar S, Yee J, Kramer H. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis 2017; 70: 737-751
18 Jiang Y, Zhang J, Yuan Y, Zha X, Xing C, Shen C, Shen Z, Qin C, Zeng M, Yang G, Mao H, Zhang B, Yu X, Sun B, Ouyang C, Xu X, Ge Y, Wang J, Zhang L, Cheng C, Yin C, Zhang J, Chen H, Ma H, Wang N. Association of increased serum leptin with ameliorated anemia and malnutrition in stage 5 chronic kidney disease patients after parathyroidectomy. Sci Rep 2016; 6: 27918
19 Jiang Y, Shen Z, Zhang J, Xing C, Zha X, Shen C, Zeng M, Yang G, Mao H, Zhang B, Yu X, Sun B, Ouyang C, Ge Y, Zhang L, Cheng C, Zhang J, Yin C, Chen H, Wang N. Parathyroidectomy increases heart rate variability and leptin levels in patients with stage 5 chronic kidney disease. Am J Nephrol 2016; 44: 245-254
20 Melamed ML, Eustace JA, Plantinga LC, Jaar BG, Fink NE, Parekh RS, Coresh J, Yang Z, Cantor T, Powe NR. Third-generation parathyroid hormone assays and all-cause mortality in incident dialysis patients: The CHOICE study. Nephrol Dial Transplant 2008; 23: 1650-1658
21 Gonzalez-Casaus ML, Gonzalez-Parra E, Sanchez-Gonzalez C, Albalate M, de la Piedra-Gordo C, Fernandez E, Torregrosa V, Rodriguez M, Lorenzo V. A lower proportion of circulating active parathyroid hormone in peritoneal dialysis does not allow the pth inter-method adjustment proposed for haemodialysis. Nefrologia 2014; 34: 330-340
22 Donadio C, Ardini M, Lucchesi A, Donadio E, Cantor T. Parathyroid hormone and large related C-terminal fragments increase at different rates with worsening of renal function in chronic kidney disease patients. A possible indicator of bone turnover status?. Clin Nephrol 2007; 67: 131-139
23 D'Amour P. Acute and chronic regulation of circulating PTH: significance in health and in disease. Clin Biochem 2012; 45: 964-969
24 Evenepoel P, Bover J, Urena Torres P. Parathyroid hormone metabolism and signaling in health and chronic kidney disease. Kidney Int 2016; 90: 1184-1190
25 Souberbielle JC, Massart C, Brailly-Tabard S, Cormier C, Cavalier E, Delanaye P, Chanson P. Serum PTH reference values established by an automated third-generation assay in vitamin D-replete subjects with normal renal function: consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients. Eur J Endocrinol 2016; 174: 315-323
26 Einbinder Y, Benchetrit S, Golan E, Zitman-Gal T. Comparison of intact pth and bio-intact pth assays among non-dialysis dependent chronic kidney disease patients. Ann Lab Med 2017; 37: 381-387
27 Taniguchi M, Tanaka M, Hamano T, Nakanishi S, Fujii H, Kato H, Koiwa F, Ando R, Kimata N, Akiba T, Kono T, Yokoyama K, Shigematsu T, Kakuta T, Kazama JJ, Tominaga Y, Fukagawa M. Comparison between whole and intact parathyroid hormone assays. Therap Apheresis Dial 2011; 15 (Suppl. 01) 42-49
28 Koda R, Kazama JJ, Matsuo K, Kawamura K, Yamamoto S, Wakasugi M, Takeda T, Narita I. Intact parathyroid hormone and whole parathyroid hormone assay results disagree in hemodialysis patients under cinacalcet hydrochloride therapy. Clin Exp Nephrol 2015; 19: 710-717
29 Connelly K, Collister D, Tangri N. Fracture risk and treatment in chronic kidney disease. Curr Opin Nephrol Hyperten 2018; 27: 221-225
30 Benson T, Menezes T, Campbell J, Bice A, Hood B, Prisby R. Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries. Osteoporos Int 2016; 27: 1817-1826
31 Guideline Working Group JSfDT . Clinical practice guideline for the management of secondary hyperparathyroidism in chronic dialysis patients. Therap Apheresis Dial 2008; 12: 514-525
32 Brossard JH, Cloutier M, Roy L, Lepage R, Gascon-Barre M, D'Amour P. Accumulation of a non-(1-84) molecular form of parathyroid hormone (PTH) detected by intact PTH assay in renal failure: importance in the interpretation of PTH values. J Clin Endocrinol Metab 1996; 81: 3923-3929
33 Brossard JH, Lepage R, Cardinal H, Roy L, Rousseau L, Dorais C, D'Amour P. Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays. Clin Chem 2000; 46: 697-703
34 Mizumura Y, Mukaiyama Y, Osada H, Hida O, Nishimiya M, Nakamura Y. The reversed ratio of 1-84 PTH (whole PTH)/intact PTH in a patient on hemodialysis associated with primary hyperparathyroidism. Clin Nephrol 2008; 69: 310-312
35 Patel S, Barron JL, Mirzazedeh M, Gallagher H, Hyer S, Cantor T, Fraser WD. Changes in bone mineral parameters, vitamin D metabolites, and PTH measurements with varying chronic kidney disease stages. J Bone Mineral Metab 2011; 29: 71-79
36 Chang JM, Lin SP, Kuo HT, Tsai JC, Tomino Y, Lai YH, Chen HC. 7-84 parathyroid hormone fragments are proportionally increased with the severity of uremic hyperparathyroidism. Clin Nephrol 2005; 63: 351-355
37 Friedman PA, Goodman WG. PTH(1-84)/PTH(7-84): A balance of power. Am J Physiol Renal Physiol 2006; 290: F975-F984
38 Sprague SM, Bellorin-Font E, Jorgetti V, Carvalho AB, Malluche HH, Ferreira A, D'Haese PC, Drueke TB, Du H, Manley T, Rojas E, Moe SM. Diagnostic accuracy of bone turnover markers and bone histology in patients with ckd treated by dialysis. Am J Kidney Dis 2016; 67: 559-566
39 D'Amour P, Brossard JH, Rousseau L, Roy L, Gao P, Cantor T. Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism. Clin Chem 2003; 49: 2037-2044