Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients

Ballinger, Angela E; Palmer, Suetonia C.; Nistor, Ionuţ; Craig, Jonathan C.; Strippoli, Giovanni F.M.

doi:10.1002/14651858.cd006254.pub2

Cited by 70 publications

(54 citation statements)

References 73 publications

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“…As previously reported, the most frequently reported adverse event in the cinacalcet group was digestive intolerance, 29 being a limitation to increasing the cinacalcet dose sufficiently to achieve serum calcium correction in some patients. Complications of subtotal parathyroidectomy depend on both surgical experience and the procedure itself.…”

Section: Discussionsupporting

confidence: 63%

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Cruzado

Moreno²,

Torregrosa

et al. 2015

JASN

123

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Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant $6 months before the study and had an eGFR.30 ml/min per 1.73 m 2 . The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

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Section: Discussionsupporting

confidence: 63%

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Cruzado

Moreno²,

Torregrosa

et al. 2015

JASN

123

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“…These effects are consistent with results from studies exploring the skeletal function of CaSR in animal models 61 (in which CaSR might enhance PTHinduced bone turnover) and with the association between a CASR polymorphism (which results in an Ala986Ser variant) and vertebral fractures in patients with primary hyperparathyroidism. 108 Chronic kidney disease Cinacalcet has been shown to reduce PTH levels in patients with chronic kidney disease 109 and to reduce the risk of requiring surgical parathyroidectomy. 110 Several small studies in patients on haemodialysis have reported that cinacalcet treatment decreased serum levels of PTH and also decreased levels of bone turn over markers; [111][112][113][114] a few of these patients developed adynamic bone.…”

Section: Primary Hyperparathyroidismmentioning

confidence: 99%

The calcium-sensing receptor in bone—mechanistic and therapeutic insights

2015

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The extracellular calcium-sensing receptor, CaSR, is a member of the G protein-coupled receptor superfamily and has a critical role in modulating Ca(2+) homeostasis via its role in the parathyroid glands and kidneys. New evidence suggests that CaSR expression in cartilage and bone also directly regulates skeletal homeostasis. This Review discusses the role of CaSR in chondrocytes, through which CaSR contributes to the development of the cartilaginous growth plate, as well as in osteoblasts and osteoclasts, through which CaSR has effects on skeletal development and bone turnover in young and mature animals. The interaction of skeletal CaSR activation with parathyroid hormone (PTH), which is secreted by the parathyroid gland, can lead to net bone formation in trabecular bone or net bone resorption in cortical bone. Allosteric modulators of CaSR are beneficial in some clinical conditions, with effects that are mediated by the ability of these agents to alter levels of PTH and improve Ca(2+) homeostasis. However, further insights into the action of CaSR in bone cells might lead to CaSR-based drugs that maximize not only the effects of the receptor on the parathyroid glands and kidneys but also on bone.

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“…13 According to a systematic review, however, cinacalcet increases risks of nausea, vomiting and hypocalcemia, suggesting harms may outweigh benefits. 14 In these cases, PTx is still needed by a significant proportion of dialysis patients with mineral disturbances. In the era of calcimimetics, surgery continues to play an important role in efficient control of renal HPT.…”

Section: Introductionmentioning

confidence: 99%

Long–term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis

Chen

Wang

et al. 2016

Renal Failure

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Parathyroidectomy (PTx) and medical treatments are both recommended for reducing serum intact parathyroid hormone (iPTH) and curing secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), but their therapeutic effects on long-term mortality are not well-known. Thus, we aim to assess such therapeutic effect of PTx. Electronic literatures published on Pubmed, Embase, and Cochrane Central Register of Controlled Trials in any language until 27 November 2015 were systematically searched. All literatures that compared outcomes (survival rate or mortality rate) between PTx-treated and medically-treated CKD patients with sHPT were included. Finally, 13 cohort studies involving 22053 patients were included. Data were extracted from all included literatures in a standard form. The outcomes of all-cause and cardiovascular mortalities were assessed using DerSimonian and Laird's random effects model. We find PTx-treated versus medically-treated patients had a 28% reduction in all-cause mortality and a 37% reduction in cardiovascular mortality. Thus, PTx versus medical treatments might reduce the risks of all-cause and cardiovascular mortalities in CKD patients with sHPT. Further studies with prospective and large-sample clinical trials are needed to find out the real effect of PTx and to assess whether mortality rates differ among patterns of PTx. ARTICLE HISTORY

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Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients

Cited by 70 publications

References 73 publications

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

The calcium-sensing receptor in bone—mechanistic and therapeutic insights

Long–term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis

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