Coen Giorgio
Ospedale Israelitico, Rome, Italy.
J Nephrol. 2008 May-Jun;21(3):313-23.
The term vitamin D is linked to the development of rickets and osteomalacia, and has been known about since at least the 17th century. Prevention of these diseases has challenged many researchers in the following centuries, which has resulted in important advances in prevention and treatment. However, it was only in 1900 that the vitamin structure was identified. In the following decades, many steps were made toward understanding the metabolism of the vitamin. Recent progress has revolutionized our view of vitamin D and suggested that it has much wider effects on the body than ever believed. In addition to its well-known effects on calcium-phosphate homeostasis, vitamin D, through its hormonal form calcitriol, has been found to be a cell-differentiating factor and antiproliferative agent with actions on a variety of tissues. By influencing gene expression, calcitriol affects many physiological processes, besides calcium-phosphate homeostasis, including muscle and keratinocyte differentiation, blood pressure regulation and the immune response. The widespread expression of 1a-hydroxylating enzyme in peripheral tissues supports the view that it exists to boost intracellular concentrations of calcitriol within some target tissues in order to modulate a unique set of genes. This new information has profound implications for chronic kidney disease (CKD) patients with their tendency to vitamin D substrate insufficiency, coupled with their documented loss of the renal 1a-hydroxylase. Administration of vitamin D receptor activators such as calcitriol have been found to favor the survival of CKD patients mainly improving the cardiovascular system. In recent years, analogs of calcitriol such as paricalcitol, able to activate the vitamin D receptor, have shown additional biologic effects and advantages compared with calcitriol in the treatment of patients with chronic renal failure.
维生素D一词与佝偻病和骨软化症的发展有关，至少从17世纪起就为人所知。在接下来的几个世纪里，预防这些疾病一直是许多研究人员面临的挑战，这也促成了预防和治疗方面的重要进展。然而，直到1900年维生素的结构才得以确定。在随后的几十年里，人们在了解维生素的代谢方面取得了许多进展。最近的进展彻底改变了我们对维生素D的看法，并表明它对身体的影响比以往认为的要广泛得多。除了其对钙磷稳态的众所周知的作用外，维生素D通过其激素形式骨化三醇，已被发现是一种细胞分化因子和抗增殖剂，对多种组织有作用。通过影响基因表达，骨化三醇除了影响钙磷稳态外，还影响许多生理过程，包括肌肉和角质形成细胞分化、血压调节和免疫反应。外周组织中1α-羟化酶的广泛表达支持了这样一种观点，即它的存在是为了提高某些靶组织内骨化三醇的细胞内浓度，从而调节一组独特的基因。这些新信息对慢性肾脏病（CKD）患者具有深远影响，因为他们有维生素D底物不足的倾向，同时还存在肾1α-羟化酶的缺失。已发现给予维生素D受体激活剂如骨化三醇有利于CKD患者的生存，主要是改善心血管系统。近年来，骨化三醇类似物如帕立骨化醇能够激活维生素D受体，在治疗慢性肾衰竭患者方面与骨化三醇相比显示出额外的生物学效应和优势。
