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

Abstract

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% cinacalcetversus 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 difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p ¼ 0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p < 0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

Combination Therapy of Denosumab and Calcitriol for a Renal Transplant Recipient with Severe Bone Loss due to Therapy-Resistant Hyperparathyroidism

“…In addition, any immediate effects of CIN on severe bone loss in this population remain unknown. Furthermore, various forms of gastrointestinal intolerance including nausea, vomiting, abdominal discomfort, and diarrhea are seen as its common adverse events (Evenepoel et al 2014), causing CIN to be not recommended for patients with IBS, such as our patient. These concerns led us to abandon the idea of prescribing CIN for our patient.…”

“…In the present case, such frequent recurrence had increased the patient's burden and eliminated his desire for repeat surgical intervention. Furthermore, the therapeutic options in place of parathyroidectomy are limited (Cohen et al 2012;Evenepoel et al 2014). Indeed, treatment with VD is difficult for patients with persistent SHPT since hypercalcemia is commonly seen in those patients.…”

“…Indeed, treatment with VD is difficult for patients with persistent SHPT since hypercalcemia is commonly seen in those patients. On the other hand, several studies have suggested that cinacalcet (CIN) offers a new treatment strategy for renal transplant recipients with persistent SHPT (Cohen et al 2012;Evenepoel et al 2014). A recent metaanalysis of 21 nonrandomized studies, including a total of 411 renal transplant recipients with persistent SHPT, showed that CIN enabled correction of hypercalcemia and decreased the PTH levels in those patients (Evenepoel et al 2014).…”

“…As far as we know, these rapid improvements cannot be achieved by treatment with parathyroidectomy or CIN (Lewin and Olgaard 2006;Evenepoel et al 2014). Therefore, we consider that DMAb has a rapid effect in recovery from bone loss with high bone resorption due to SHPT in patients with CKD.…”

“…Persistent SHPT is known to cause bone loss, bone pain, and fracture. Moreover, it has been demonstrated that persistent SHPT is associated with poor graft function and adverse cardiovascular outcomes (Egbuna et al 2007;Covic et al 2009;Evenepoel et al 2014). Therefore, adequate management of persistent SHPT after RT is a critical issue.…”