Department of Internal Medicine, University Medical Center Groningen, The Netherlands.
Curr Drug Targets. 2011 Jan;12(1):42-53. doi: 10.2174/138945011793591572.
Prevention of progressive renal function loss and its complications remains the main challenge in clinical nephrology. Although current therapeutic strategies aiming at reduction of blood pressure and proteinuria often slow down deterioration of renal function, still many patients progress to end-stage renal disease. The development of novel pharmacological approaches for treatment of chronic kidney disease (CKD) is therefore instrumental. Here we review the renoprotective potential of vitamin D and its analogues. In CKD patients, vitamin D deficiency is common and progression of CKD is associated with low (active) vitamin D levels. Moreover, in animal models of CKD, treatment with vitamin D (analogues) alone or in combination with renin-angiotensin-aldosterone system (RAAS) blockade reduces proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. Potential underlying mechanisms include suppression of the RAAS, modulation of immune cell function and direct protective effects on renal cells such as podocytes. Whether vitamin D analogues could further optimize existing therapies in human renal disease is currently under investigation.
预防肾功能进行性丧失及其并发症仍然是临床肾脏病学的主要挑战。尽管目前旨在降低血压和蛋白尿的治疗策略通常可减缓肾功能恶化,但仍有许多患者进展为终末期肾病。因此,开发治疗慢性肾脏病 (CKD) 的新型药理学方法非常重要。在这里,我们综述了维生素 D 及其类似物的肾保护潜力。在 CKD 患者中,维生素 D 缺乏很常见,CKD 的进展与低(活性)维生素 D 水平有关。此外,在 CKD 动物模型中,单独使用维生素 D(类似物)或与肾素-血管紧张素-醛固酮系统 (RAAS) 阻断剂联合治疗可减少蛋白尿、肾小球硬化和肾小管间质纤维化。潜在的机制包括抑制 RAAS、调节免疫细胞功能以及对肾脏细胞(如足细胞)的直接保护作用。维生素 D 类似物是否可以进一步优化人类肾脏疾病的现有治疗方法,目前正在研究中。