Jean Guillaume, Lafage-Proust Marie-Hélène, Massy Ziad A, Drüeke Tilman B
Centre de rein artificiel, néphrologie et dialyse, 69160 Tassin-La-Demi-Lune, France.
Nephrol Ther. 2009 Nov;5(6):520-32. doi: 10.1016/j.nephro.2009.07.010. Epub 2009 Sep 12.
The vitamin D hormonal system is involved in the regulation of more than 800 genes. Vitamin D deficiency, which is evaluated on the basis of the serum level of 25-hydroxycholecalciferol (25[OH]D), is frequently observed in the general population, particularly in patients with chronic kidney disease (CKD). Vitamin D deficiency is associated with an increased risk of falls and fracture and also with diabetes, malignancies, autoimmune diseases, depression and mortality. Furthermore, CKD is accompanied by a decrease in the renal production of 1,25 dihydroxycholecalciferol (1,25OHD). Such deficiencies have also been implicated in the pathophysiology of secondary hyperparathyroidism. Currently, vitamin D supplementation is not recommended in stage 5 CKD. However, since there is also significant extra-renal production of 1,25(OH)(2)D this would appear to be in favour of vitamin D treatment. We describe the disturbances of vitamin D metabolism occurring in CKD and discuss the advantages and the potential toxicity risk of vitamin D supplementation as well as the optimal serum 25[OH]D level. We then present the pharmacological properties of the various medicinal forms of vitamin D derivates and suggest therapeutic guidelines for supplementation with 25(OH)D(3) or cholecalciferol. We also examine existing guidelines for the administration of active 1-alpha-hydroxylated vitamin D. Despite the absence of strong scientific support by randomized controlled intervention studies, vitamin D supplementation should be considered in patients with CKD stages 4-5D having vitamin D insufficiency or deficiency, for the prevention of secondary hyperparathyroidism and for other potential benefits owing to its pleiotropic effects.
维生素D激素系统参与800多个基因的调控。根据血清25-羟基胆钙化醇(25[OH]D)水平评估的维生素D缺乏在普通人群中经常出现,尤其是在慢性肾脏病(CKD)患者中。维生素D缺乏与跌倒和骨折风险增加相关,还与糖尿病、恶性肿瘤、自身免疫性疾病、抑郁症及死亡率有关。此外,CKD伴有肾脏1,25-二羟基胆钙化醇(1,25[OH]₂D)生成减少。这些缺乏也与继发性甲状旁腺功能亢进的病理生理学有关。目前,不建议在5期CKD患者中补充维生素D。然而,由于1,25(OH)₂D也有显著的肾外生成,这似乎支持维生素D治疗。我们描述了CKD中发生的维生素D代谢紊乱,讨论了维生素D补充的益处和潜在毒性风险以及最佳血清25[OH]D水平。然后我们介绍了各种维生素D衍生物剂型的药理特性,并提出了补充25(OH)D₃或胆钙化醇的治疗指南。我们还研究了活性1-α-羟基化维生素D给药的现有指南。尽管缺乏随机对照干预研究的有力科学支持,但对于CKD 4-5D期且存在维生素D不足或缺乏的患者,应考虑补充维生素D,以预防继发性甲状旁腺功能亢进,并因其多效性作用获得其他潜在益处。