Early and Severe Hyperparathyroidism Associated with Hypercalcemia After Renal Transplant Treated with Cinacalcet

Abstract

Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and preexisting bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with posttransplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level.

Measuring Total Blood Calcium Displays a Low Sensitivity for the Diagnosis of Hypercalcemia in Incident Renal Transplant Recipients

“…Control of serum calcium may be achieved by a parathyroidectomy, but this often occurs at the expense of transient or persistent hypoparathyroidism (41,42). Data from several small series indicate that treatment with cinacalcet, a calcimimetic, might be an attractive alternative for the treatment of hypercalcemia in renal transplant recipients (43)(44)(45)(46)(47)(48)(49). A randomized, double-blind, placebo-controlled study has been initiated to evaluate the efficacy and safety of using cinacalcet to correct hypercalcemia in incident renal transplant recipients with autonomous hyperparathyroidism (EudraCT 207-000573-29).…”

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

“…Cinacalcet (Sensipar 1 / Mimpara 1 ; Amgen Inc., Thousand Oaks, CA), an allosteric modulator of the CaSR, has demonstrated efficacy in decreasing calcium and PTH in patients with secondary HPT on dialysis (21); and in a number of small, open-label, single arm, single-center and retrospective studies, cinacalcet decreased serum calcium and PTH and increased serum phosphorus levels in renal transplant recipients with persistent HPT (22)(23)(24)(25)(26)(27)(28). In these studies, cinacalcet was well tolerated with no evidence of adverse effects on immunosuppressive therapy or allograft function.…”

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“…7 About 45% to 50% of patients have secondary hyperparathyroidism 1 year after successful transplant. 3 In our study group, in which median followup after transplant was 17.5 months, we found persistent hyperparathyroidism in 34% of our patients after successful transplant.…”

“…2 About 45% to 50% of patients have persistence of secondary hyperparathyroidism at 1 year after successful transplant. 3 The severity of posttransplant secondary hyperparathyroidism may range from an asymptomatic state of "inappropriate parathyroid hormone secretion," to a more critical situation of refractoriness of parathyroid glands, to any form as a result of medical treatment, known as tertiary hyper parathyroidism. Previous studies in adult renal transplant recipients have suggested that the duration of dialysis treatment and the development of nodular and/or monoclonal hyperplasia of parathyroid glands are the most important factors determining the degree of secondary hyperparathyroidism after renal transplant.…”

“…4 Chronic steroid treatment, "pulse" steroid therapy for acute rejection, calcineurin inhibitors, hyperlipidemia, and obesity are reported as additional factors. 3 Our aim was to examine PTH levels in children after transplant and to determine the clinical and biochemical risk factors of persistent hyperparathyroidism.…”