Cross Talk Between the Renin-Angiotensin-Aldosterone System and Vitamin D-FGF-23-klotho in Chronic Kidney Disease
Cross Talk Between the Renin-Angiotensin-Aldosterone System and Vitamin D-FGF-23-klotho in Chronic Kidney Disease
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DOI：
10.1681/asn.2010121251
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发表时间：
2011-09-01
影响因子：
13.6
通讯作者：
Navis, Gerjan
中科院分区：
文献类型：
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作者：
de Borst, Martin H.;Vervloet, Marc G.;Navis, Gerjan
越来越多的证据表明，维生素D、成纤维细胞生长因子23和Klotho之间的相互作用形成了钙磷代谢的内分泌轴，而这一轴的紊乱参与了肾脏疾病的进展。最近的几项研究也证明了维生素D对肾素基因的负调控。在慢性肾脏疾病(CKD)中，由于1-α羟基酶的丢失而导致低水平的骨化三醇，增加了肾脏肾素的产生。肾素-血管紧张素-醛固酮系统(RAAS)的激活反过来又减少了Klotho的肾脏表达，Klotho是正确传递成纤维细胞生长因子-23信号的关键因素。由此产生的高水平的成纤维细胞生长因子-23抑制了1-α羟化酶，进一步降低了骨化三醇。这种反馈循环导致维生素D缺乏、RAAS激活、高水平的成纤维细胞生长因子-23和肾脏Klotho缺乏，所有这些都与肾脏损害的进展有关。在这里，我们研究了RAAS和维生素D-FGF23-Klotho轴之间相互作用的现有证据，以及它对CKD进展的可能影响。
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.