Cozzolino Mario, Bernard Laurence, Csomor Philipp A
Renal Division and Laboratory of ExperimentalNephrology, Department of Health Sciences, University of Milan, Milan, Italy.
Department of Biometrics, Vifor Pharma Ltd, Geneva, Switzerland.
Clin Kidney J. 2021 May 28;14(11):2437-2443. doi: 10.1093/ckj/sfab091. eCollection 2021 Nov.
This study evaluates the effects of active (1α-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT).
A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with ≥30 participants per arm and ≥6 weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0).
Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16 weeks to 2 years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 µg (two studies); the weekly dose of alfacalcidol was 1.75-7.0 µg. Across all studies, rates of hypercalcaemia were 1.1-43.3% with AVD versus 0-3.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P < 0.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust.
Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT.
本研究评估活性（1α-羟化）维生素D（AVD）治疗对非透析慢性肾脏病（ND-CKD）和继发性甲状旁腺功能亢进（SHPT）患者高钙血症的影响。
对PubMed、Embase和Cochrane图书馆数据库进行系统检索（截至2020年5月14日），以确定在患有ND-CKD和SHPT的成人中进行的单药口服AVD治疗的随机、安慰剂对照试验。仅纳入每组≥30名参与者且持续时间≥6周的研究。感兴趣的结局是发生高钙血症发作的受试者数量。使用综合Meta分析软件（3.0版）对符合条件的研究进行Meta分析。
共纳入6项研究（5项评估帕立骨化醇，1项评估阿法骨化醇），涉及799例患者。治疗持续时间为16周至2年。帕立骨化醇的每周给药剂量为7μg（3项研究）和14μg（2项研究）；阿法骨化醇的每周剂量为1.75 - 7.0μg。在所有研究中，AVD治疗组的高钙血症发生率为1.1% - 43.3%，而安慰剂组为0 - 3.4%。对这6项研究的Meta分析表明，与安慰剂相比，AVD导致高钙血症的可能性高6.6倍（优势比：6.63，95%置信区间：2.37，18.55；P < 0.001）。两项单独的敏感性分析（一项排除了被确定为具有高偏倚风险的研究；第二项排除了占观察到的高钙血症事件很大比例的两项研究）表明，主要的Meta分析结果是可靠的。
与安慰剂相比,AVD显著增加了ND-CKD合并SHPT患者发生高钙血症的风险。
