Effects of parathyroidectomy on plasma PTH fragments and heart rate variability in stage 5 chronic kidney disease patients

Chen, Huimin; Ren, Wenkai; Gao, Zhenzhen; Zhang, Ming; Tang, Shaowen; Xu, Fan; Huang, Yaoyu; Zhang, Lína; Chen, Ying; Yang, Guang; Qian, Haoliang; Zhou, Wenbin; Ouyang, Chun; Gao, Xueyan; Zhang, Jing; Xiao, Yujie; Zhao, Baiqiao; Wang, Jing; Bian, Anning; Li, Fan; Wan, Huiting; Gao, Wei; Wang, Xiaoyun; Xing, Changying; Zhang, Xiaoming; Wang, Ningning

doi:10.1080/0886022x.2021.1931318

Cited by 6 publications

(8 citation statements)

References 48 publications

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“…In the Ussing chamber setups, samples were treated with 1 ng/ml PTH 1–34, 1 ng/ml heat‐inactivated PTH 1–34, 20 ng/ml FGF‐23, 20 ng/ml heat‐inactivated FGF‐23, 20 ng/ml FGF‐23 plus 1 ng/ml PTH 1–34, 1 ng/ml PTH 1–34 with 1 µmol/l PTHrP 7–34 (PTHR antagonist; PromoCell GmbH, Heidelberg, Germany), or 20 ng/ml FGF‐23 with 1 µmol/l PD173074 (FGFR antagonist; Abcam, Cambridge, UK) for 150 min for the Mg 2+ transport study. The concentrations of direct FGF‐23 and PTH 1–34 incubations were comparable to high physiological serum concentrations which were previously reported (Chen et al, 2021 ; Urakawa et al, 2006 . The concentrations of antagonists were reported previously (Khuituan et al, 2012 ; Laohapitakworn et al, 2011 ; Maycas et al, 2015 ).…”

Section: Methodssupporting

confidence: 87%

Fibroblast growth factor‐23 and parathyroid hormone suppress small intestinal magnesium absorption

Suksridechacin

Thongon

2022

Physiological Reports

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In the present study, we examined the systemic and direct effects of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) on duodenal, jejunal, and ileal Mg 2+ absorption. The rats were injected with FGF-23 or PTH for 5 h before collecting the duodenum, jejunum, and ileum for Mg 2+ transport analysis in Ussing chambers. The duodenum, jejunum, and ileum were directly exposed to FGF-23, PTH, or FGF-23 plus PTH with or without cell signaling inhibitors for 150 min in Ussing chambers prior to performing the Mg 2+ transport study.The small intestinal tissues were also subjected to western blot analyses for FGF receptor (FGFR), PTH receptor (PTHR), Klotho, transient receptor potential melastatin 6 (TRPM6), and cyclin as well as the cystathionine βsynthase domain divalent metal cation transport mediator 4 (CNNM4) expression. The small intestine abundantly expressed FGFR and PTHR proteins, whereas, Klotho was not expressed in rat small intestine. Systemic PTH or FGF-23 injection significantly suppressed transcellular Mg 2+ transport in the duodenum and jejunum. Direct FGF-23-, PTH-, or FGF-23 plus PTH exposure also suppressed transcellular Mg 2+ absorption in the duodenum and jejunum. There was no additional inhibitory effect of PTH and FGF-23 on intestinal Mg 2+ absorption. The inhibitory effect of PTH, FGF-23, or FGF-23 plus PTH was abolished by Gö 6850. Systemic PTH-or FGF-23-injection significantly decreased membranous TRPM6 expression, but increased cytosolic CNNM4 expression in the duodenum, jejunum, and ileum. In the present study, we propose a novel magnesiotropic action of PTH and FGF-23 by modulating small intestinal Mg 2+ absorption.

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Section: Methodssupporting

confidence: 87%

Fibroblast growth factor‐23 and parathyroid hormone suppress small intestinal magnesium absorption

Suksridechacin

Thongon

2022

Physiological Reports

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“…Clinical studies have confirmed the importance of treating SHPT in improving renal anemia in hemodialysis patients [9,48] . Zingraff et al [49] have demonstrated that successful PTX can significantly improve anemia in SHPT patients, consistent with the conclusions in our previous reports [9,50] . In this study, PTX patients(n=28) were followed up over three months after the surgery (median time: 6.88 months).…”

Section: Discussionmentioning

confidence: 91%

“…We have demonstrated that stage 5 CKD patients with severe SHPT had more significant anemia, which was significantly improved after parathyroidectomy (PTX) [9] . Cross-sectional studies suggest that there may be a link between biomarkers of mineral metabolism and hemoglobin (Hb) [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Relationship between blood bone metabolic biomarkers and anemia in CKD patients

Fan

Yang

et al. 2022

Preprint

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Introduction: Blood bone metabolic biomarkers are non-invasive indexes for evaluating renal osteodystrophy (ROD). Here the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients are investigated, the effects of parathyroidectomy (PTX) on above indices are analyzed. Methods: In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) subgroup with PTX, were enrolled. A prospective study with 28 PTX patients was followed up. The degree of anemia was classified as mild, moderate, and severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83g/L and 102g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23) and a-klotho were tested. Results: The mean eGFR in CKD patients was 25.74+-35.99 ml/min/1.73 m2 and 84.10% patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86+-5.99g/L, 92.71+-5.96g/L and 67.38+-10.56g/L, respectively. CKD patients had higher adjusted Ca, P, ALP, iPTH and FGF23 levels, and lower a-klotho levels than controls. Baseline adjusted Ca, P, iPTH and a-klotho levels were associated with Hb in CKD patients. Blood adjusted Ca, P, iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH and FGF23 levels were ameliorated, while a-klotho levels increased. Conclusions: Blood adjusted Ca, P, iPTH and a-klotho levels were correlated with Hb in CKD patients, correcting ROD is supposed to be therapeutic targets for anemia. Keywords: Anemia; Chronic kidney disease-mineral and bone disorder; Bone metabolic biomarkers; Parathyroidectomy; Secondary hyperparathyroidism

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“…Previous studies had shown that the 3 rd /2 nd ratio differed among diseases, though most of them focused on one disease group at one time. This ratio was 0.60–0.62 in patients with CKD in different studies [ 15 – 17 ], whereas the ratio in patients with PHPT was 0.60–0.64 [ 8 , 18 ]. Only in one single-center observational study, these two assays were performed among different patient groups, showing that the medium 3 rd /2 nd ratio for hemodialysis patients, renal transplantation recipients, patients with PHPT, patients with parathyroid carcinoma (PC), and healthy elderly people (median age was 72.6 years) was 0.74, 0.77, 0.76, 1.16, and 0.80, respectively [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Full-length versus intact PTH concentrations in pseudohypoparathyroidism type 1 and primary hyperparathyroidism: clinical evaluation of immunoassays in individuals from China

Yang

Song

et al. 2022

Endocrine

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Purpose The application of the third-generation parathyroid hormone (PTH) assay [PTH(1–84) assay] for evaluating PTH levels in patients with pseudohypoparathyroidism type-1 (PHP1) is less popular than the second-generation assay. Therefore, we aimed at examining the conformity between the PTH(1–84) assay and the intact PTH (iPTH) assay, specifically examining their performance in individuals with PHP1 versus individuals with primary hyperparathyroidism (PHPT), compared to healthy controls. Methods PTH(1–84) and iPTH assay were performed in patients with PHP1, patients with PHPT, and healthy volunteers. ∆PTH%, PTH(1–84)/iPTH (3 rd /2 nd ratio), iPTH/upper limit of normal (ULN), and PTH (1–84)/ULN of each group were calculated for comparison. Linear regression, Kappa conformity test, and Bland–Altman analysis of ∆PTH/mean of iPTH and PTH(1–84) (percent bias) plotted against the mean of iPTH and PTH(1–84) were performed to determine the conformance of PTH(1–84) assay with iPTH assay. Results A total of 54 patients with PHP1, 127 patients with PHPT, and 65 healthy volunteers were enrolled in this study. All the three groups showed strong linear relationship between iPTH and PTH (1–84) ( r 2 = 0.9661, 0.7733, and 0.9575, respectively). No significant differences were noted in 3 rd /2 nd ratio (median 0.76 vs. 0.72) between the PHP1 and PHPT groups ( p > 0.05). Conformity examination showed the Kappa value was 0.778 and 0.395 for PHP1 and PHPT groups respectively. No difference in the Kappa values was found between PHP1A and PHP1B subgroups. Bland–Altman plot demonstrated that the proportion of data points that were plotted within mean ± 1.96 SD in PHP1, PHPT and normal control groups were 96.3%, 93.7%, and 98.5%, respectively. The mean percent bias of the three groups were 26.1%, 31.2%, and 17.0%, respectively. The range of mean ± 1.96 SD of percent bias of the three groups were 2.2%–50.0%, −14.3%–76.6%, and 6.7%–27.2%, respectively. Conclusion Although iPTH and PTH(1–84) values were both lower in the present PHP1 cohort than in the PHPT cohort, there appear to be differences in the relative agreement between both immunoassays, and in the relationship between the two values, especially in comparison to healthy controls. Whether these differences are due to differential accumulation of C-terminal fragments or other factors requires further study.

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Effects of parathyroidectomy on plasma PTH fragments and heart rate variability in stage 5 chronic kidney disease patients

Cited by 6 publications

References 48 publications

Fibroblast growth factor‐23 and parathyroid hormone suppress small intestinal magnesium absorption

Fibroblast growth factor‐23 and parathyroid hormone suppress small intestinal magnesium absorption

Relationship between blood bone metabolic biomarkers and anemia in CKD patients

Full-length versus intact PTH concentrations in pseudohypoparathyroidism type 1 and primary hyperparathyroidism: clinical evaluation of immunoassays in individuals from China

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