背景:糖尿病肾病(DKD)与心血管疾病(CVD)的高风险相关。己酮可可碱(PTF),一种具有抗炎作用的非选择性磷酸二酯酶抑制剂,抗增殖,和抗纤维化作用,在临床试验和荟萃分析中都证明了肾脏的益处。本工作旨在研究PTF对糖尿病和中度至重度慢性肾脏疾病(CKD)患者亚临床动脉粥样硬化(SA)进展的影响。
方法:在此开放标签中,随机对照,前瞻性单中心试点研究确定了102例2型糖尿病和CKD患者的颈动脉内中膜厚度(CIMT)和踝肱指数(ABI)的演变,18个月内服用阿司匹林或对照组。我们还确定了炎症标志物和Klotho(KL)水平的变化,一种维持心血管健康的蛋白质,以及它们与SA进展的关系。
结果:接受PTF治疗的患者表现出更好的CIMT演变,外周血细胞(PBC)中KLmRNA水平升高,炎症状态降低。CIMT值的进展与血清中KL和PBC中mRNA表达水平的变化成反比。多元回归分析表明,PTF处理和PBCs中KLmRNA表达的变化,连同HDL的变化,是CIMT进展的显著决定因素(校正后R2=0.24,P<0.001),与传统危险因素无关。此外,这两个变量构成了对CIMT最差进展的保护因素[OR:0.103(P=0.001)和0.001(P=0.005),分别]。
结论:PTF降低了CIMT变异评估的SA进展,与PBC中KL基因表达相关的有益作用。
背景:研究方案代码为PTF-AA-TR-2009,该试验已在欧盟药物监管机构临床试验(EudraCT#2009-016595-77)上注册。验证日期为2010-03-09。
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.
BACKGROUND: 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.