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      Severe hypercalcaemia early after kidney transplantation in two patients with severe secondary hyperparathyroidism previously treated with etelcalcetide

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          Abstract

          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.

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

          J M Cruzado, P. Moreno, J. V. Torregrosa … (2016)
          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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            Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism : Two Randomized Clinical Trials

            Geoffrey A. Block, David A. Bushinsky, John Cunningham … (2017)
            Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease.
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              Parathyroidectomy after successful kidney transplantation: a single centre study.

              Yves Vanrenterghem, Pieter Evenepoel, F M Debruyne … (2007)
              Successful kidney transplantation is believed to cure secondary hyperparathyroidism, but persistent disease has emerged in a significant number of allograft recipients. A parathyroidectomy is ultimately required in some of these patients. To gain insight into the incidence, risk factors and consequences of parathyroidectomy in patients with a functioning renal graft, we performed a retrospective case-controlled study. Charts of 1743 recipients of a kidney allograft, transplanted between 1989 and 2004, were reviewed. Patients with a functioning graft subjected to parathyroidectomy were identified. Their charts were checked for various demographic, clinical and biochemical variables. The data were compared with those obtained from patients transplanted in the same period, but not subjected to parathyroidectomy (controls). Persistent hyperparathyroidism in patients with a functioning graft requiring parathyroidectomy developed in 90 patients, corresponding to an overall parathyroidectomy rate of 8.89 per 1000 person-years at risk. Female gender (OR 1.79, P < 0.05) and higher pre-transplant serum concentrations of PTH (OR per 1 ng/l increase, 1.003, P < 0.0001) and calcium (OR per 1 mg/dl increase, 2.58, P < 0.0001) were identified as independent predictors of post-transplant parathyroidectomy. A significant increase of the serum creatinine was observed after parathyroidectomy (1.91 +/- 0.72 vs 1.76 +/- 0.63 mg/dl, P < 0.01). Graft survival, however, was similar in cases and controls. Persistent hyperparathyroidism requiring parathyroidectomy after successful renal transplantation is a common clinical problem. Female patients with a high pre-transplant serum level of PTH and calcium are especially at risk. Although graft function deteriorates shortly after parathyroidectomy, graft survival, overall, is not different from controls.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Kidney J
                Journal ID (iso-abbrev): Clin Kidney J
                Journal ID (publisher-id): ckj
                Title: Clinical Kidney Journal
                Publisher: Oxford University Press
                ISSN (Print): 2048-8505
                ISSN (Electronic): 2048-8513
                Publication date Collection: August 2021
                Publication date (Electronic): 17 March 2021
                Publication date PMC-release: 17 March 2021
                Volume: 14
                Issue: 8
                Pages: 1977-1979
                Affiliations
                [1 ] Department of Nephrology, Cliniques Universitaires Saint-Luc , Brussels, Belgium
                [2 ] Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain , Brussels, Belgium
                [3 ] Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc , Brussels, Belgium
                Author notes
                Correspondence to: Arnaud Devresse; E-mail: arnaud.devresse@ 123456uclouvain.be
                Author information
                https://orcid.org/0000-0002-1668-975X
                https://orcid.org/0000-0003-4133-881X
                https://orcid.org/0000-0001-7369-7812
                Article
                Publisher ID: sfab063
                DOI: 10.1093/ckj/sfab063
                PMC ID: 8323146
                PubMed ID: 34345422
                SO-VID: f3ed8601-fd1a-41fe-a331-855562b1ff49
                Copyright © © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Date received : 04 January 2021
                Date: 15 March 2021
                Page count
                Pages: 3
                Categories
                Subject: Exceptional Cases
                Subject: AcademicSubjects/MED00340

                ScienceOpen disciplines: Nephrology
                Keywords: calcimimetics,etelcalcetide,haemodialysis,hypercalcaemia,kidney transplant,parathyroidectomy
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: calcimimetics, etelcalcetide, haemodialysis, hypercalcaemia, kidney transplant, parathyroidectomy

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