五氧嘧啶可改善 2 型糖尿病和慢性肾病患者亚临床动脉粥样硬化的进展:一项随机试验。

IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Javier Donate-Correa, Carla M Ferri, Carmen Mora-Fernández, Nayra Pérez-Delgado, Ainhoa González-Luis, Juan F Navarro-González
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引用次数: 0

摘要

背景:糖尿病肾病(DKD)与较高的心血管疾病(CVD)风险有关。五氧去氧肾上腺素(Pentoxifylline,PTF)是一种非选择性磷酸二酯酶抑制剂,具有抗炎、抗增生和抗纤维化作用,在临床试验和荟萃分析中均证明对肾脏有益。本研究旨在研究 PTF 对糖尿病和中重度慢性肾病(CKD)患者亚临床动脉粥样硬化(SA)进展的影响:在这项开放标签、随机对照、前瞻性的单中心试点研究中,我们测定了 102 名 2 型糖尿病和 CKD 患者的颈动脉内膜厚度(CIMT)和踝肱指数(ABI)的变化情况,这些患者被分配到 PTF、阿司匹林或对照组,为期 18 个月。我们还测定了炎症标志物和 Klotho(KL)(一种参与维持心血管健康的蛋白质)水平的变化及其与 SA 进展的关系:结果:接受 PTF 治疗的患者的 CIMT 变化较好,外周血细胞(PBCs)中的 KL mRNA 水平升高,炎症状态减轻。CIMT值的变化与血清中KL的变化和外周血细胞中mRNA的表达水平成反比。多元回归分析表明,PTF 治疗和 PBCs 中 KL mRNA 表达的变化以及 HDL 的变化是 CIMT 进展的重要决定因素(调整后 R2 = 0.24,P 结论):PTF可减少以CIMT变化评估的SA进展,这种有益效应与PBCs中KL基因的表达有关:研究方案代码为 PTF-AA-TR-2009,该试验已在欧盟药物管理局临床试验注册(EudraCT #2009-016595-77)。验证日期为 2010-03-09。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

Background: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD).

Methods: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA.

Results: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively].

Conclusions: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs.

Trial registration: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

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来源期刊
Cardiovascular Diabetology
Cardiovascular Diabetology 医学-内分泌学与代谢
CiteScore
12.30
自引率
15.10%
发文量
240
审稿时长
1 months
期刊介绍: Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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