Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
PLoS Med. 2013;10(4):e1001436. doi: 10.1371/journal.pmed.1001436. Epub 2013 Apr 30.
Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting.
Cochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89-1.05]), had imprecise effect on cardiovascular mortality (0.67 [0.16-2.87]), and prevented parathyroidectomy (0.49 [0.40-0.59]) and hypercalcemia (0.23 [0.05-0.97]), but increased hypocalcemia (6.98 [5.10-9.53]), nausea (2.02 [1.45-2.81]), and vomiting (1.97 [1.73-2.24]). Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients.
Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population.
钙敏感受体激动剂可降低慢性肾脏病（CKD）患者的甲状旁腺激素水平，但治疗对患者相关结局的影响尚不确定。我们进行了系统评价和荟萃分析，以总结钙敏感受体激动剂治疗 CKD 成人患者的获益和危害，并使用累积荟萃分析来确定在这一临床环境中钙敏感受体治疗证据的发展情况。
通过电子检索 Cochrane 和 Embase 数据库（截至 2013 年 2 月 7 日），以确定评估钙敏感受体治疗对 CKD 成人患者死亡率和不良事件影响的随机试验。两名独立的审查员识别试验、提取数据并评估偏倚风险。18 项试验纳入 7446 名参与者，比较了西那卡塞加常规治疗与安慰剂或无治疗加常规治疗在 CKD 成人患者中的效果。在 CKD 5D 期（透析）的中高质量证据（基于推荐评估、制定与评估分级标准）中，西那卡塞对全因死亡率几乎没有影响（相对风险，0.97[95%置信区间，0.89-1.05]），对心血管死亡率的影响不明确（0.67[0.16-2.87]），预防甲状旁腺切除术（0.49[0.40-0.59]）和高钙血症（0.23[0.05-0.97]），但增加低钙血症（6.98[5.10-9.53]）、恶心（2.02[1.45-2.81]）和呕吐（1.97[1.73-2.24]）。在 CKD 3-5 期的成人中，临床结局数据稀疏。平均而言，在 CKD 5D 期的 1000 名患者中治疗 1 年对生存率没有影响，可预防约 3 名患者发生甲状旁腺切除术，而 60 名患者出现低钙血症，150 名患者出现恶心。分析受到 CKD 3-5 期和肾移植受者数据不足的限制。
西那卡塞可降低 CKD 5D 患者甲状旁腺切除术的需求，但似乎不能改善全因或心血管死亡率。在 CKD 5D 期进一步的试验不太可能改变我们对西那卡塞在该人群中的治疗效果的信心。
