Acute and Severe Hypercalcemia Early After Kidney Transplantation in a Patient Previously Treated With Etelcalcetide (original) (raw)
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Clinical Kidney Journal, 2021
Cinacalcet and, more recently, etelcalcetide revolutionized the treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney transplant (KT) usually improves CKD–MBD. However, a significant proportion of KT recipients have high serum calcium levels, not requiring any treatment. We report two patients previously treated with etelcalcetide who developed severe (>3.3 mmol/L) hypercalcaemia in the early post-KT course, requiring parathyroidectomy. Pathological studies showed parathyroid adenomas and hyperplasia. One patient had a graft biopsy showing numerous intratubular calcium phosphate crystals. These observations should prompt pharmacovigilance studies and careful follow-up of KT recipients previously treated with etelcalcetide.
Transplantation Proceedings, 2009
Background. Secondary hyperparathyroidism (SHPT) is a relevant problem in patients undergoing dialysis, and cinacalcet hydrochloride seems to be the best option for controlling it. After kidney transplantation (KTx), moderate to severe SHPT may persist and cause hypercalcemia and hypophosphatemia, among other deleterious effects. The number of patients receiving cinacalcet before KTx is increasing. Objective. To evaluate the evolution of calcemia, phosphatemia, and intact parathyroid hormone (iPTH) after KTx in patients with SHPT receiving cinacalcet on dialysis.
Treatment of Hyperparathyroidism with Cinacalcet in Kidney Transplant Recipients
Transplantation Journal, 2010
Background. After successful kidney transplantation, hyperparathyroidism can persist in 10%-50% of patients and can harmfully affect bone metabolism. Calcimimetic cinacalcet is a new treatment option in the management of persistent hyperparathyroidism in these patients. Methods. This prospective, clinical study of 11 patients included those who had a serum intact parathyroid hormone (iPTH) concentration Ͼ65 ng/L, a serum creatinine concentration was Ͻ200 mol/L, stable kidney graft function, and were Ͼ1 year since transplantation. Patients were not treated with drugs other than calcitriol that could influence bone metabolism. During the 6-month observation period, in which the stability of measured parameters was determined, and in the 12-month treatment period (cinacalcet 30 mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine, vitamin 25OH D 3 , bone-specific alkaline phosphatase (ALP), osteocalcin, collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral density (BMD). Results. During the treatment period, the serum calcium concentration decreased significantly (from 2.50 Ϯ 0.12 to 2.32 Ϯ 0.12 mmol/L; P Ͻ .01). Serum iPTH concentration decreased significantly (from 247 [range, 199-362] at time 0 to 198 [range, 165-233] ng/L after 1 month of treatment; P Ͻ .05), but increased slightly thereafter. After 6 months of treatment, the serum concentration of ALP and CTX increased significantly, but decreased thereafter. There were no significant changes in the other parameters assessed. Renal function remained stable during the treatment period. The BMD of the lumbar spine, hip, and forearm did not change during the 12 months of treatment. Conclusion. Cinacalcet was effective in treating posttransplant hyperparathyroidism, resulting in decreased calcemia and transient decreased iPTH. ALP and CTX transiently increased during therapy, but other markers of bone metabolism remained unchanged. Twelve months of cinacalcet treatment did not result in a change in BMD. Cinacalcet seems to be a safe drug with no negative effect on renal function.
Kidney International Reports, 2017
Introduction: The pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisted of a single dose part and a multiple dose (3 times weekly for 4 weeks) part. Major inclusion criteria were hemodialysis for at least 90 days, serum intact parathyroid hormone (iPTH) $ 300 pg/ml, and serum albumin-corrected Ca (cCa) $ 9.0 mg/dl. There were 3 single-dose cohorts (n ¼ 6 each) randomized 2:1 to 5, 10, or 20 mg etelcalcetide or placebo, and 2 multiple-dose cohorts (n ¼ 11 each) randomized 8:3 to 2.5 or 5 mg etelcalcetide or placebo. Results: Etelcalcetide plasma concentration decreased rapidly after i.v. administration, generally remained stable from 24 hours postdose to the next dialysis, and then decreased by dialysis. Etelcalcetide exposure increased dose proportionally. Etelcalcetide plasma predialysis concentration reached almost steady state at week 4. A single dose of etelcalcetide dose-dependently reduced serum iPTH in 30 minutes, and the reduction reached a plateau at 1 hour that lasted until 8 hours. The percent change from baseline serum iPTH thereafter showed a trend to gradually decrease; it was still À30% or greater on day 3. Similar results were obtained at the last injection (days 27-29) of the multiple dose. The effect of the multiple dose was sustained during the interdialytic period. Etelcalcetide decreased serum cCa in a more gradual but dose-dependent and sustained manner. Discussion: Etelcalcetide dose-dependently reduced serum iPTH and serum cCa. Moreover, the effect was sustained in the interdialytic period.
PLOS ONE, 2019
Background Calcimimetics have been shown to be effective and safe therapies for the treatment of secondary hyperparathyroidism (sHPT), a serious complication of disordered mineral metabolism associated with dialysis-dependent chronic kidney disease. Etelcalcetide, a recently approved intravenous calcimimetic, reduces serum parathyroid hormone (PTH), calcium, phosphorus, and fibroblast growth factor-23 concentrations. Here we report the first integrated safety profile of etelcalcetide using pooled data from five pivotal clinical trials. Methods This analysis included data from patients receiving hemodialysis with moderate to severe sHPT enrolled in two randomized, placebo-controlled trials; a randomized active-controlled (with cinacalcet) trial; and two single-arm, open-label extension trials. Patients initially received etelcalcetide intravenously 5 mg three times weekly (TIW) after hemodialysis; with potential dose increases of 2.5 or 5 mg at 4-week intervals to a maximum dose of 15 mg TIW, depending on serum PTH and calcium levels. The nature, frequency, and severity of treatment-emergent adverse events (AEs) and changes in laboratory parameters were assessed. Results Overall, we evaluated 1023 patients from the placebo-controlled trials, 683 from the activecontrolled trial, and 1299 from open-label extensions. The frequency and nature of common treatment-emergent AEs reported for the etelcalcetide arm were consistent among the placebo-controlled and active-controlled trials. The most common AEs were those related to mineral metabolism (decreased blood calcium, hypophosphatemia, muscle spasms) or gastrointestinal abnormalities (diarrhea, nausea, vomiting). Hypocalcemia leading to discontinuation of either calcimimetic was experienced in � 1% of patients.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2014
Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value<10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p<0.001. There was no statistical differ...
Nephrology Dialysis Transplantation, 2005
Background. Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism. The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients. Methods. Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet. The total study time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10-2.60 mmol/l. Results. Serum calcium decreased significantly from 2.73±0.05 mmol/l to 2.44±0.05 and 2.42± 0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients reached the target range rapidly and remained normocalcaemic throughout the study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10, respectively, compared with week 0. Serum phosphate increased. Renal function remained stable and no allograft rejection was observed. From weeks 2 to 10, daily cinacalcet doses administered were 30 mg (n ¼ 8), 15 mg (n ¼ 1) and 60 mg (n ¼ 1), respectively. Conclusion. Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation. It appears to be safe. Thus, cinacalcet represents a promising alternative for parathyroidectomy in these patients.
Endocrine Journal, 1993
We report a male who exhibited the Landry-Guillain-Barre syndrome and hypercalcemia. He initially exhibited normocalcemia, followed by hypercalcemia which developed during tetraplegia and the recovering phase of the syndrome. The administration of prednisolone, saline, calcitonin, etidronate, and indomethacin failed to normalize the serum calcium level. Since, with mobilization, the serum calcium level gradually became normal, the calcium abnormality was misdiagnosed as immobilization hypercalcemia. However, among 6 different parathyroid hormone (PTH) assays used, including a two-site immunoradiometric assay, only a mid-region specific PTH (mPTH) assay showed high levels in both hypercalcemic and normocalcemic periods, and a high level of mPTH was not suppressed by calcium infusion in the normocalcemic period. Neck exploration disclosed a parathyroid adenoma weighed 100 mg. This case illustrates the hypercalcemia-inducing effect of immobilization on mild type primary hyperparathyroidism. A high level mPTH assay, its unsuppressibility by the calcium infusion test, and ineffectiveness of oral etidronate for hypercalcemia were valuable in differentiating hypercalcemia due to primary hyperparathyroidism from that resulting solely from prolonged immobilization.
Extreme hypercalcemia in a kidney transplant recipient
CEN case reports, 2018
Post-transplant hypercalcemia is a major problem in renal transplant recipients, which may negatively affect both graft and patient survival. In this paper, we present a 66-year-old male kidney transplant recipient, who was admitted to our clinic with symptoms of fever, nausea, vomiting and lethargy. Laboratory data showed good renal function; however, a serum calcium level of 22.1 mg/dL. The patient was treated by isotonic saline together with furosemide and methylprednisolone. Because of treatment resistance, subcutaneous calcitonin and ibandronate were added to the treatment protocol as well. Since all these medications were not effective, hemodialysis with low-calcium (1.25 mmol/L) dialysate was applied for three consecutive days, which resulted in normalization of serum calcium. Several investigations were carried out for diagnosing the underlying etiology. Positron-emission tomography (PET)/CT revealed a strong diffuse uptake of FDG in the bones and spleen. A bone marrow biops...