Palmer Suetonia C, McGregor David O, Craig Jonathan C, Elder Grahame, Macaskill Petra, Strippoli Giovanni Fm
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Harvard Institute of Medicine, Room 550, 4 Blackfan Street, Boston, MA, USA, 02115.
Cochrane Database Syst Rev. 2009 Oct 7(4):CD005633. doi: 10.1002/14651858.CD005633.pub2.
Clinical guidelines recommend vitamin D compounds to suppress serum parathyroid hormone (PTH) in chronic kidney disease (CKD), however treatment may be associated with increased serum phosphorus and calcium, which are associated with increased mortality in observational studies. Observational data also indicate vitamin D therapy may be independently associated with reduced mortality in CKD.
We assessed the effects of vitamin D compounds on clinical, biochemical, and bone outcomes in people with CKD and receiving dialysis.
We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of retrieved articles.
Randomised controlled trials (RCTs) in subjects with CKD and requiring dialysis that assessed treatment with vitamin D compounds.
Data was extracted by two authors. Results are summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).
Sixty studies (2773 patients) were included. No formulation, route, or schedule of administration was associated with altered risks of death, bone pain, or parathyroidectomy. Marked heterogeneity in reporting of outcomes resulted in few data available for formal meta-analysis. Compared with placebo, vitamin D compounds lowered serum PTH at the expense of increasing serum phosphorus. Trends toward increased hypercalcaemia and serum calcium did not reach statistical significance but may be clinically relevant. Newer vitamin D compounds (paricalcitol, maxacalcitol, doxercalciferol) lowered PTH compared with placebo, with increased risks of hypercalcaemia, although inadequate data were available for serum phosphorus. Intravenous vitamin D may lower PTH compared with oral treatment, and be associated with lower serum phosphorus and calcium levels, although limitations in the available studies precludes a conclusive statement of treatment efficacy. Few studies were available for intermittent versus daily and intraperitoneal versus oral administration or directly comparative studies of newer versus established vitamin D compounds.
AUTHORS' CONCLUSIONS: We confirm that vitamin D compounds suppress PTH in people with CKD and requiring dialysis although treatment is associated with clinical elevations in serum phosphorus and calcium. All studies were inadequately powered to assess the effect of vitamin D on clinical outcomes and until such studies are conducted the relative importance of changes in serum PTH, phosphorus and calcium resulting from vitamin D therapy remain unknown. Observational data showing vitamin D compounds may be associated with improved survival in CKD need to be confirmed or refuted in specifically designed RCTs.
临床指南推荐使用维生素D化合物来抑制慢性肾脏病（CKD）患者的血清甲状旁腺激素（PTH），然而治疗可能会导致血清磷和钙升高，在观察性研究中，这与死亡率增加相关。观察性数据还表明，维生素D治疗可能与CKD患者死亡率降低独立相关。
我们评估了维生素D化合物对接受透析的CKD患者的临床、生化及骨骼结局的影响。
我们检索了Cochrane肾脏组专业注册库、Cochrane对照试验中心注册库（CENTRAL）、MEDLINE、EMBASE以及检索文章的参考文献列表。
针对需要透析的CKD受试者进行的评估维生素D化合物治疗的随机对照试验（RCT）。
由两位作者提取数据。结果以二分类结局的风险比（RR）或连续性结局的均值差（MD）及95%置信区间（CI）进行汇总。
纳入了60项研究（2773例患者）。没有哪种制剂、给药途径或给药方案与死亡、骨痛或甲状旁腺切除术风险的改变相关。结局报告中存在显著异质性，导致可用于正式荟萃分析的数据很少。与安慰剂相比，维生素D化合物降低了血清PTH，但代价是血清磷升高。高钙血症和血清钙升高的趋势未达到统计学显著性，但可能具有临床相关性。与安慰剂相比，新型维生素D化合物（帕立骨化醇、马沙骨化醇、度骨化醇）降低了PTH，但高钙血症风险增加，不过关于血清磷的数据不足。与口服治疗相比，静脉注射维生素D可能会降低PTH，并与较低的血清磷和钙水平相关，尽管现有研究存在局限性，无法对治疗效果作出确定性陈述。关于间歇性给药与每日给药、腹膜内给药与口服给药，或新型与已上市维生素D化合物的直接对比研究，可用的研究很少。
我们证实，维生素D化合物可抑制需要透析的CKD患者的PTH，尽管治疗会导致血清磷和钙在临床上升高。所有研究的样本量均不足以评估维生素D对临床结局的影响，在进行此类研究之前，维生素D治疗导致的血清PTH、磷和钙变化的相对重要性仍然未知。观察性数据显示维生素D化合物可能与CKD患者生存率提高相关，这需要在专门设计的RCT中得到证实或反驳。
