Amino terminal cleavage of PTH(1–84) to PTH(7–84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients

Koshikawa, Masao; Nishiguchi, Kensuke; Yorifuji, Soshi; Shimazu, Keiji; Takaori, Koji; Mori, Keita; Eguchi, Eriko; Okada, Kikuo; Tanaka, Atsuo; Kubo, Takashi

doi:10.1007/s10157-010-0264-5

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…In the present clinical trial, we showed that cholecalciferol treatment was efficient to normalize the serum levels of 25(OH)D and decrease PTH levels in patients supplemented compared to placebo group, suggesting that adequacy of vitamin D status might have modulated synthesis this hormone in parathyroid cells and this effect might have contributed to lower bone reabsorption [12]. In respect to the serum FGF-23 in cholecalciferol group, the significant difference detected by the group-time interaction analysis might be due to the higher production of this hormone by osteocytes, since vitamin D administration upregulates FGF-23 [13, 28].…”

Section: Discussionmentioning

confidence: 92%

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

et al. 2017

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It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.

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Section: Discussionmentioning

confidence: 92%

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

et al. 2017

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“…Interestingly, circulating 7-84 PTH fragments are generated not only by the peripheral metabolism of 1-84 PTH, but they are also secreted, in a Ca-dependent manner, by the PT glands; it appears that the CaSR is involved [54,58]. The results of initial studies investigating the clinical role of the 1-84 PTH/7-84 PTH ratio, in which a low ratio (relatively high proportion of 7-84 PTH) was associated with low bone turnover, have proven to be inconsistent and not clinically useful [59][60][61].…”

Section: Pth Fragmentsmentioning

confidence: 97%

Parathyroid hormone and growth in chronic kidney disease

Waller

2010

Pediatr Nephrol

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Growth failure is common in children with chronic kidney disease, and successful treatment is a major challenge in the management of these children. The aetiology is multi-factorial with "chronic kidney disease-metabolic bone disorder" being a key component that is particularly difficult to manage. Parathyroid hormone is at the centre of this mineral imbalance, consequent skeletal disease and, ultimately, growth failure. When other aetiologies are treated, good growth can be achieved throughout the course of the disease when parathyroid hormone (PTH) levels are in the normal range or slightly elevated. A direct correlation between PTH levels and growth has not been convincingly established, and the direct effect of PTH on growth has not been adequately described; furthermore, direct actions of PTH on the growth plate are unproven. The effects of PTH on growth stem from the pivotal role that PTH plays in the development of renal osteodystrophy. In severe secondary hyperparathyroidism, the growth plate is altered and growth is affected. At the other end of the spectrum, with an over-suppressed parathyroid gland, the rate of bone turnover and remodelling is markedly diminished, and some data suggest this is associated with poor growth. Most of the data available suggests that avoiding the development of significant bone disease through the strict control of PTH levels permits good growth. Absolute optimal ranges for PTH that maximise growth or minimise growth failure are not yet established.

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“…Regarding the determination method, despite the available immunoassays showing important differences in absolute values (37), we observed that the relative change induced by cinacalcet treatment was fully comparable between the 3 kits used (2 of them measuring iPTH and 1 specific for PTH 1-84, ie, whole PTH, also known as biointact). Previous studies had already suggested that cinacalcet reduces not only iPTH but also whole PTH and the whole PTH to iPTH ratio (38) and that it also changes the regulation of N-terminal PTH cleavage by calcium concentration (39,40).…”

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confidence: 99%

Pharmacodynamics of Cinacalcet Over 48 Hours in Patients With Controlled Secondary Hyperparathyroidism: Useful Data in Clinical Practice

Arenas

Fuente

Delgado

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

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In hemodialysis patients with secondary hyperparathyroidism controlled by cinacalcet, a transient (1-6 hours) reduction in PTH and P and an increase in calcitonin are observed after each daily dose, with return to baseline at 24 hours. After calcimimetics discontinuation, PTH was significantly increased at 48 hours. The assay used to measure PTH does not influence relative changes induced by cinacalcet.

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Amino terminal cleavage of PTH(1–84) to PTH(7–84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients

Cited by 3 publications

References 27 publications

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial

Parathyroid hormone and growth in chronic kidney disease

Pharmacodynamics of Cinacalcet Over 48 Hours in Patients With Controlled Secondary Hyperparathyroidism: Useful Data in Clinical Practice

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