Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic kidney disease: the VALIDATE-D study.
Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic kidney disease: the VALIDATE-D study.
复制标题
评估糖尿病肾脏疾病中维生素D受体激动剂治疗的激素机制：验证-D研究。
DOI：
10.1186/1472-6823-13-33
复制
发表时间：
2013-08-23
影响因子：
2.7
通讯作者：
Vaidya A
中科院分区：
文献类型：
--
作者：
Brown JM;Secinaro K;Williams JS;Vaidya A
Insufficient vitamin D status and increased renin-angiotensin system (RAS) activity have been associated with renal-vascular disease and nephropathy in diabetes. Accumulating evidence indicates that vitamin D receptor (VDR) activation lowers unfavorable RAS activity; however, more human intervention studies evaluating whether this mechanism could influence diabetic kidney disease are needed. We previously reported that both vitamin D levels and genetic variation at the VDR predict human RAS activity, and that vitamin D therapy can lower RAS activity in non-diabetics. The VALIDATE-D study is a randomized, placebo-controlled, intervention study designed to extend these findings by evaluating whether direct VDR activation in diabetes lowers circulating and local renal-vascular tissue RAS activity (Aims 1 and 2) in a manner similar to the action of ACE inhibitors (Aim 3). Forty subjects with type 2 diabetes, microalbuminuria, and without chronic kidney disease will be recruited to undergo detailed assessment of the RAS before and after randomization to calcitriol 0.75 mcg/day or placebo. Primary analyses will evaluate whether calcitriol therapy reduces circulating and renal-vascular tissue-RAS activity in comparison to placebo. All subjects will thereafter be treated with lisinopril and followed for 3.5 months to evaluate whether combination therapy (calcitriol + lisinopril vs. placebo + lisinopril) additively or synergistically improves renal-vascular function, and lowers proteinuria. The VALIDATE-D study is the first human intervention study to evaluate whether direct VDR activation can lower the human RAS in diabetes, compared to the effect of an ACE inhibitor, and whether this mechanism can translate to clinically relevant endpoints for diabetic kidney disease. The outcomes of VALIDATE-D will have major implications for the recommendation of vitamin D supplementation for the primary prevention of kidney complications in diabetes. ClinicalTrials.gov, NCT01635062
登录
查看更多内容
影响因子：
15.9
作者：
REDGRAVE, J;RABINOWE, S;WILLIAMS, GH
通讯作者：
WILLIAMS, GH
影响因子：
4.2
作者：
Sairanen, S;Kärkkäinen, M;Välimäki, MJ
通讯作者：
Välimäki, MJ
影响因子：
5
作者：
Wang L;Ma J;Manson JE;Buring JE;Gaziano JM;Sesso HD
通讯作者：
Sesso HD
影响因子：
13.2
作者：
de Boer, Ian H.;Ioannou, George N.;Weiss, Noel S.
通讯作者：
Weiss, Noel S.
影响因子：
13.6
作者：
Mallamaci, Francesca;Ruggenenti, Piero;Zoccali, Carmine
通讯作者：
Zoccali, Carmine