Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial.
Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial.
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DOI：
10.1371/journal.pone.0205831
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Jalal D
中科院分区：
文献类型：
--
作者：
Andrews ES;Perrenoud L;Nowak KL;You Z;Pasch A;Chonchol M;Kendrick J;Jalal D
慢性肾病（CKD）-矿物质和骨病（MBD）是一种导致血管钙化和加速动脉粥样硬化的全身性疾病。尿酸已被证明与血管钙化和颈动脉内膜中层厚度 (CIMT) 相关，并抑制 1 α-羟化酶，导致 1,25-二羟基维生素 D (1,25(OH)2D) 水平降低和完整甲状旁腺激素 (iPTH) 水平升高。我们假设降低血清尿酸会降低 CKD 中的 CIMT、钙化倾向和 CKD-MBD 循环标志物。这是一项随机、双盲研究的事后分析，研究对象为 80 名患有 3 期 CKD 和高尿酸血症的患者，这些患者接受别嘌呤醇或安慰剂治疗 12 周。 CIMT和T50分别作为血管疾病和血清钙化倾向的标志物进行测量。测量了以下 CKD-MBD 标志物：血清钙、磷、维生素 D 代谢物、iPTH 和成纤维细胞生长因子 23 (FGF-23)。对研究参与者的内皮细胞中肾外 1α-羟化酶的表达进行了评估。与安慰剂相比，别嘌呤醇成功降低了血清尿酸水平，估计值为-3.3 mg/dL（95% C.I. -4.1，-2.5；p < 0.0001）。然而，12 周后，我们发现 CIMT 或血清 T50 没有显着变化。维生素 D 代谢物、iPTH、FGF-23 或内皮 1α-羟化酶的表达没有显着变化。这些数据表明，尿酸以外的因素可能在 CKD-MBD 的调节中发挥更重要的作用，包括 CKD 患者的血管钙化和维生素 D 代谢。
Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.
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影响因子：
1.2
作者：
HISATOME, I;ISHIMURA, M;MASHIBA, H
通讯作者：
MASHIBA, H
影响因子：
3.4
作者：
CAMERON, JS;SIMMONDS, HA
通讯作者：
SIMMONDS, HA
DOI：
10.1053/j.ajkd.2012.07.021
发表时间：
2013-01
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Jalal DI;Chonchol M;Chen W;Targher G
通讯作者：
Targher G
影响因子：
4.3
作者：
Byon, Chang Hyun;Chen, Yabing
通讯作者：
Chen, Yabing
影响因子：
9.8
作者：
Chen, Wei;Roncal-Jimenez, Carlos;Lanaspa, Miguel;Smits, Gerard;Chonchol, Michel;Johnson, Richard J.;Jalal, Diana
通讯作者：
Jalal, Diana