Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease
Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease
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DOI：
10.1038/ki.2010.543
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发表时间：
2011-04-01
影响因子：
19.6
通讯作者：
Tokumoto, Masanori
中科院分区：
文献类型：
--
作者：
Dusso, Adriana S.;Tokumoto, Masanori
在肾脏疾病中，肾脏产生维生素D激素骨化三醇的能力的进行性丧失是甲状旁腺激素（PTH）升高以及矿物质和骨骼疾病的关键因素，这些疾病易导致肾脏和心血管损伤、异位钙化和高死亡率。因此，几十年来，安全纠正骨化三醇缺乏以抑制PTH一直是治疗的选择。然而，最近的流行病学和实验数据表明，骨化三醇替代可能通过与PTH抑制无关的肾脏和心脏保护作用改善结局。此外，维生素D缺乏症在肾脏疾病中的发生率惊人，并且比骨化三醇缺乏症与肾脏疾病进展和死亡的风险更高。尽管这些发现具有转化相关性，但目前尚无前瞻性试验支持维生素D补充和/或骨化三醇替代治疗安全停止/缓解肾脏疾病进展的疗效。这篇综述更新了恶性循环背后的病理生理学，肾损伤损害了正常维生素D和骨化三醇水平的维持，这反过来又阻碍了维生素D/骨化三醇肾保护作用，这是前瞻性试验设计的一个要求，以改善目前在肾脏疾病的所有阶段进行维生素D干预的建议。Kidney International（2011）79，715-729; doi：10.1038/ki.2010.543; 2011年1月26日在线发表
In kidney disease, the progressive loss of renal capacity to produce calcitriol, the vitamin D hormone, is a key contributor to elevations in parathyroid hormone (PTH) and mineral and skeletal disorders predisposing to renal and cardiovascular damage, ectopic calcifications, and high mortality rates. Thus, the safe correction of calcitriol deficiency to suppress PTH has been the treatment of choice for decades. However, recent epidemiological and experimental data suggest that calcitriol replacement may improve outcomes through renal and cardioprotective actions unrelated to PTH suppression. Furthermore, a striking incidence of vitamin D deficiency occurs in kidney disease and associates more strongly than calcitriol deficiency with a higher risk for kidney disease progression and death. Despite the translational relevance of these findings, no prospective trials are currently available in support of the efficacy of vitamin D supplementation and/or calcitriol replacement to safely halt/moderate renal disease progression. This review updates the pathophysiology behind the vicious cycle by which kidney injury impairs the maintenance of normal vitamin D and calcitriol levels, which in turn impedes vitamin D/calcitriol renoprotective actions, a requirement for the design of prospective trials to improve current recommendations for vitamin D interventions at all stages of kidney disease. Kidney International (2011) 79, 715-729; doi: 10.1038/ki.2010.543; published online 26 January 2011