Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Medicine (RMH), The University of Melbourne, Melbourne, Victoria, Australia.
Intern Med J. 2019 Jan;49(1):48-54. doi: 10.1111/imj.14036.
Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres.
To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet.
We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24- and 12-month period, respectively, from cessation of cinacalcet.
A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27-90) pmol/L to 85 (interquartile range 41-139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92-176) IU/L to 143 (102-197) IU/L (P < 0.0001).
Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12-month period following withdrawal of cinacalcet. Longer-term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity.
慢性肾脏病中的继发性甲状旁腺功能亢进症（SHPT）与心血管和骨骼病理学有关。为了达到甲状旁腺激素（PTH）目标值并控制与 SHPT 相关的生化异常，需要采用复杂的治疗方法，而严重的 SHPT 通常需要甲状旁腺切除术或钙敏感受体激动剂西那卡塞。在澳大利亚，西那卡塞于 2009 年至 2015 年期间为透析患者提供公共资金，随后 EVOLVE 研究的发表导致大多数接受西那卡塞治疗的患者停止了治疗，此后该药物的资金被撤回。我们在澳大利亚肾脏中心检查了与这一变化相关的临床和生化结果。
评估透析患者停止使用西那卡塞后的生化和临床结果变化。
我们对 11 个澳大利亚单位中 2015 年 8 月后停止使用西那卡塞的透析患者进行了回顾性研究。分别在停止使用西那卡塞后 24 个月和 12 个月评估临床结局和生化参数的变化。
共纳入 228 例患者（占单位所有透析患者的 17.7%）。患者年龄为 63 ± 15 岁，其中 182 例接受血液透析，46 例接受腹膜透析。停止使用西那卡塞后 24 个月内，我们观察到 26 例甲状旁腺切除术、3 例钙化防御、8 例骨折和 50 例死亡。8 例患者因特殊准入计划符合条件而重新开始使用西那卡塞。停止使用西那卡塞后 12 个月时的生化变化包括血清 PTH 从基线时的 54（四分位距 27-90）pmol/L 增加到 85（四分位距 41-139）pmol/L（P < 0.0001）、血清钙从 2.3 ± 0.2 mmol/L 增加到 2.5 ± 0.1 mmol/L（P < 0.0001）和碱性磷酸酶从 123（92-176）IU/L 增加到 143（102-197）IU/L（P < 0.0001）。
停止使用西那卡塞后 12 个月内，血清 PTH、钙和碱性磷酸酶显著增加。长期随访将确定这些生化和治疗变化是否与甲状旁腺切除术和心血管死亡率和发病率的改变有关。
