Persistent hyperparathyroidism in renal allograft recipients: Vitamin D receptor, calcium-sensing receptor, and apoptosis

Taniguchi, Masatomo; Tokumoto, Masanori; Matsuo, Dai; Motoyama, Kentaro; Sugitani, Atsushi; Kuroki, Shin-Ichiro; Yotsueda, Hideki; Tsuruya, Kazuhiko; Hirakata, Hideki; Iida, Mitsuo

doi:10.1038/sj.ki.5001549

Cited by 59 publications

(54 citation statements)

References 37 publications

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“…Regression of parathyroid hyperplasia has been reported in rare cases of spontaneous infarction of the glands [6,7]. In addition, enhanced apoptosis of parathyroid cells has been observed in diffuse hyperplasia after kidney transplantation, suggesting the possibility of regression in the long term [8].In the past, the capacity of calcitriol therapy to induce regression of parathyroid hyperplasia had been a matter of debate. In a study of oral calcitriol pulse therapy, given to chronic haemodialysis patients, we observed a significant decrease in the mean ± SD volume of parathyroid glands (from 0.87 ± 0.32 to 0.51 ± 0.23 cm 3 ) after 12 weeks of treatment, with a concomitant significant reduction in intact PTH levels [9].…”

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confidence: 99%

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Komaba

Fukagawa

2008

Nephrology Dialysis Transplantation

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Secondary hyperparathyroidism is one of the most common and serious complications of chronic kidney disease (CKD). The main factors responsible for excessive synthesis and secretion of parathyroid hormone (PTH) include phosphate retention, hypocalcaemia and calcitriol deficiency resulting from decreased kidney function [1,2]. Sustained hypersecretion of PTH is associated with an increase in the parathyroid gland size, initially leading to diffuse parathyroid hyperplasia. Subsequently, some cells in the parathyroid glands proliferate in a monoclonal growth pattern, and the enlarged glands exhibit an advanced type of nodular hyperplasia [3]. In the course of parathyroid hyperplasia, both calcium-sensing receptors (CaSR) and vitamin D receptors (VDR) are progressively down-regulated [4,5], which results in diminished responsiveness of parathyroid glands with nodular hyperplasia to active vitamin D treatment.Conversely, whether regression of parathyroid hyperplasia can occur has remained a matter of discussion. Regression of parathyroid hyperplasia has been reported in rare cases of spontaneous infarction of the glands [6,7]. In addition, enhanced apoptosis of parathyroid cells has been observed in diffuse hyperplasia after kidney transplantation, suggesting the possibility of regression in the long term [8].In the past, the capacity of calcitriol therapy to induce regression of parathyroid hyperplasia had been a matter of debate. In a study of oral calcitriol pulse therapy, given to chronic haemodialysis patients, we observed a significant decrease in the mean ± SD volume of parathyroid glands (from 0.87 ± 0.32 to 0.51 ± 0.23 cm 3 ) after 12 weeks of treatment, with a concomitant significant reduction in intact PTH levels [9]. In contrast, Quarles et al. failed to observe a decrease in the parathyroid gland size after 36 weeks of intermittent intravenous or oral calcitriol treatments [10]; the mean ± SD gland volume was 1.9 ± 0.6 and 2.1 ± Correspondence and offprint requests to:

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confidence: 99%

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Komaba

Fukagawa

2008

Nephrology Dialysis Transplantation

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“…Pretransplant PTH and calcium levels can also predict the severity of persistent hyperparathyroidism and the need for parathyroid surgery after transplantation [18] . Restoration of CaSR and VDR expression after successful transplantation which can allow the shrinkage of gland size is expected only in nonnodular hyperplastic glands [19] . Due to the long life span of parathyroid cells (approximately 20 years) with a cell renewal rate of only 5% per year, the decrease in PTH level after the first 3 mo occurs at a very slow rate.…”

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confidence: 99%

Mineral and bone disorder after kidney transplantation

Taweesedt

Disthabanchong

2015

WJT

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After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.

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“…The CaSR play a key role in the excessive cell proliferation in PTG hyperplasia (17,18,19,20,21,22,23). In humans, the regression of PTG hyperplasia has been reported rarely, in cases of spontaneous infarction of the glands (24,25) and in cases of DH after kidney transplantation (26,27).…”

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confidence: 99%

Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy

Vulpio

Bossola

Stasio

et al. 2013

European Journal of Endocrinology

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Background: Cinacalcet is a new effective treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients (HP), but the alterations of parathyroid gland (PTG) hyperplasia determined by cinacalcet and vitamin D have not been extensively investigated in humans. Methods: We performed histological analyses of 94 PTGs removed from 25 HP who underwent parathyroidectomy (PTx) because of SHPT refractory to therapy with vitamin D alone (group AZ13 HP and 46 PTGs) or associated with cinacalcet (group BZ12 HP and 48 PTGs). The number, weight, the macroscopic cystic/hemorrhagic changes, and type of hyperplasia of PTG (nodularZNH, diffuseZDH) were assessed. In randomly selected HP of group A (4 HP and 14 PTGs) and group B (4 HP and 15 PTGs), the labeling index of cells positive to Ki-67 and TUNEL and the semiquantitative score of immunohistochemistry staining of vitamin D receptor, calcium-sensing receptor, and vascular endothelial growth factor-a (VEGF-a) were measured in the entire PTGs and in the areas with DH or NH. Results: The number and weight of single and total PTG of each HP were similar in the two groups as well as the number of PTG with macroscopic cystic/hemorrhagic areas. TUNEL, Ki-67, and VEGF-a scores were higher in NH than in DH areas. Conclusion: This observational study of a highly selected population of HP, submitted to PTx because SHPT refractory to therapy, shows that the macroscopic, microscopic, and immunochemistry characteristics of PTG in HP who received or did not receive cinacalcet before PTx did not differ significantly.

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Persistent hyperparathyroidism in renal allograft recipients: Vitamin D receptor, calcium-sensing receptor, and apoptosis

Cited by 59 publications

References 37 publications

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Regression of parathyroid hyperplasia by calcimimetics--fact or illusion?

Mineral and bone disorder after kidney transplantation

Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy

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