Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

摘要 背景：移植术后持续性甲状旁腺功能亢进与心血管事件、骨折及死亡风险升高相关。本研究旨在对比两种可选治疗方案：甲状旁腺切除术（parathyroidectomy, PTX）与拟钙剂西那卡塞（calcimimetic agent cinacalcet）。
方法：本研究为单中心回顾性研究，纳入因持续性甲状旁腺功能亢进引发高钙血症的成年肾移植受者。纳入标准：移植术后任意时间检测到甲状旁腺激素（parathyroid hormone, PTH）＞65 pg/mL且血清钙＞11.5 mg/dL，或移植术后1年血清钙持续高于10.2 mg/dL。将接受西那卡塞治疗的患者（n=46）与接受甲状旁腺切除术治疗的患者（n=30）进行对比，随访周期为1年。分析临床与实验室数据，以对比两种治疗方式的疗效与安全性。
结果：甲状旁腺切除术组的血钙控制速度更快（第1个月vs第6个月），且在第12个月时血钙水平显著更低（9.1±1.2 vs 9.7±0.8 mg/dL，p＜0.05）；该组患者的血清磷水平显著更高（3.8±1.0 vs 2.9±0.5 mg/dL，p＜0.05），且甲状旁腺激素水平恢复至正常范围（45±51 pg/mL）。尽管西那卡塞在长期可控制血钙与血磷水平，但仅能降低而无法使甲状旁腺激素恢复正常（197±97 pg/mL）。西那卡塞组中仍有95%的患者甲状旁腺激素高于正常范围，而甲状旁腺切除术组仅为22%。西那卡塞治疗患者的肾功能更佳（肌酐1.2±0.3 vs 1.7±0.7 mg/dL，p＜0.05）。
结论：尽管长期来看手术治疗会伴随肾功能恶化，但在纠正甲状旁腺功能亢进的代谢紊乱方面，手术治疗优于西那卡塞。西那卡塞被证实为一种安全且耐受性良好的药物。