Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen and University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
J Am Soc Nephrol. 2011 Sep;22(9):1603-9. doi: 10.1681/ASN.2010121251. Epub 2011 Aug 18.
There is increasingly evidence that the interactions between vitamin D, fibroblast growth factor 23 (FGF-23), and klotho form an endocrine axis for calcium and phosphate metabolism, and derangement of this axis contributes to the progression of renal disease. Several recent studies also demonstrate negative regulation of the renin gene by vitamin D. In chronic kidney disease (CKD), low levels of calcitriol, due to the loss of 1-alpha hydroxylase, increase renal renin production. Activation of the renin-angiotensin-aldosterone system (RAAS), in turn, reduces renal expression of klotho, a crucial factor for proper FGF-23 signaling. The resulting high FGF-23 levels suppress 1-alpha hydroxylase, further lowering calcitriol. This feedback loop results in vitamin D deficiency, RAAS activation, high FGF-23 levels, and renal klotho deficiency, all of which associate with progression of renal damage. Here we examine current evidence for an interaction between the RAAS and the vitamin D-FGF-23-klotho axis as well as its possible implications for progression of CKD.
越来越多的证据表明，维生素 D、成纤维细胞生长因子 23（FGF-23）和 klotho 之间的相互作用形成了钙和磷代谢的内分泌轴，该轴的紊乱导致肾脏疾病的进展。最近的几项研究还表明维生素 D 对肾素基因有负向调节作用。在慢性肾脏病（CKD）中，由于 1-α羟化酶的丧失，导致活性维生素 D 水平降低，从而增加肾脏肾素的产生。肾素-血管紧张素-醛固酮系统（RAAS）的激活反过来又降低了 klotho 的肾脏表达，klotho 是 FGF-23 信号传导的关键因素。由此产生的高 FGF-23 水平抑制 1-α羟化酶，进一步降低活性维生素 D。这种反馈循环导致维生素 D 缺乏、RAAS 激活、高 FGF-23 水平和肾脏 klotho 缺乏，所有这些都与肾脏损害的进展有关。在这里，我们检查了 RAAS 和维生素 D-FGF-23-klotho 轴之间相互作用的现有证据及其对 CKD 进展的可能影响。
