Tillmann Frank-Peter, Wächtler Carolin, Hansen Anita, Rump Lars Christian, Quack Ivo
Klinik für Nephrologie, Heinrich Heine Universität Düsseldorf, Moorenstr. 5, D-40225, Düsseldorf, Germany.
Transplant Res. 2014 Dec 31;3(1):21. doi: 10.1186/s13737-014-0021-5. eCollection 2014.
The effects of pre-transplantation medication for secondary hyperparathyroidism on post-transplantation parathyroid hormone (PTH) and calcium levels have not yet been conclusively determined. Therefore, this study sought to determine the level of off-label use of cinacalcet and to determine predictors of its administration during the long-term follow-up of a cohort of individuals who received deceased-donor renal transplants. Furthermore, safety considerations concerning the off-label use of cinacalcet are addressed.
This was a case-control study of 355 stable renal transplant recipients. The patient cohort was divided into two groups. Transplant group A comprised patients who did not receive cinacalcet treatment, and transplant group B comprised patients who received cinacalcet treatment during follow-up after renal transplantation. The characteristics of the patients were evaluated to determine predictors of cinacalcet use after successful renal transplantation.
Compared with the control individuals (n = 300), the cinacalcet-treated individuals (n = 55) had significantly higher PTH levels at 4 weeks post-transplantation (20.3 ± 1.6 versus 40.7 ± 4.0 pmol/L, p = 0.0000) when they were drug naive. At 3.2 years post-transplantation, cinacalcet-treated patients showed higher PTH (26.2 ± 2.3 versus 18.4 ± 2.3 pmol/L, p = 0.0000), higher calcium (2.42 ± 0.03 versus 2.33 ± 0.01 mmol/L, p = 0.0045) and lower phosphate (0.95 ± 0.04 versus 1.06 ± 0.17 mmol/L, p = 0.0021) levels. Individuals in the verum group were more likely to receive cinacalcet therapy (45.5% versus 14.3%, p = 0.0000), and they had higher pill burdens for the treatment of hyperparathyroidism (1.40 ± 0.08 versus 0.72 ± 0.03 pills per patient, p = 0.0000) whilst they were on the waiting list for transplantation. Regression analysis confirmed the associations between hypercalcaemic hyperparathyroidism and PTH levels at 4 weeks post-transplantation (p = 0.0001), cinacalcet use (p = 0.0000) and the preoperative total pill burden (p = 0.0000). Renal function was the same in both groups.
Parathyroid gland dysfunction pre-transplantation translates into clinically relevant hyperparathyroidism post-transplantation, despite patients being administered more intensive treatment whilst on dialysis. PTH levels at 4 weeks post-transplantation might serve as a marker for the occurrence of hypercalcaemic hyperparathyroidism during follow-up.
移植前治疗继发性甲状旁腺功能亢进的药物对移植后甲状旁腺激素（PTH）和钙水平的影响尚未最终确定。因此，本研究旨在确定西那卡塞的超说明书使用情况，并确定在一组接受 deceased-donor 肾移植个体的长期随访期间其使用的预测因素。此外，还讨论了西那卡塞超说明书使用的安全性问题。
这是一项对 355 名稳定肾移植受者的病例对照研究。患者队列分为两组。移植 A 组包括未接受西那卡塞治疗的患者，移植 B 组包括肾移植后随访期间接受西那卡塞治疗的患者。评估患者特征以确定肾移植成功后西那卡塞使用的预测因素。
与对照组个体（n = 300）相比，接受西那卡塞治疗的个体（n = 55）在移植后 4 周时，当他们未用过药时，PTH 水平显著更高（20.3±1.6 对 40.7±4.0 pmol/L，p = 0.0000）。移植后 3.2 年，接受西那卡塞治疗的患者显示出更高的 PTH（26.2±2.3 对 18.4±2.3 pmol/L，p = 0.0000）、更高的钙（2.42±0.03 对 2.33±0.01 mmol/L，p = 0.0045）和更低的磷（0.95±0.04 对 1.06±0.17 mmol/L，p = 0.0021）水平。试验组个体更有可能接受西那卡塞治疗（45.5%对 14.3%，p = 0.0000），并且在等待移植期间治疗甲状旁腺功能亢进的药丸负担更高（每位患者 1.40±0.08 对 0.72±0.03 片，p = 0.0000）。回归分析证实了高钙血症性甲状旁腺功能亢进与移植后 4 周时的 PTH 水平（p = 0.0001）、西那卡塞使用（p = 0.0000）和术前总药丸负担（p = 0.0000）之间的关联。两组的肾功能相同。
移植前甲状旁腺功能障碍转化为移植后临床上相关的甲状旁腺功能亢进，尽管患者在透析期间接受了更强化的治疗。移植后 4 周时的 PTH 水平可能作为随访期间高钙血症性甲状旁腺功能亢进发生的标志物。
