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长五聚素 3 作为终末期肾病多种危险因素的广谱生物标志物:与全因死亡率的关联。

Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality.

机构信息

UCIBIO, REQUIMTE, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias Saúde (IINFACTS), Gandra-Paredes, Portugal.

出版信息

Mediators Inflamm. 2019 Jun 16;2019:3295725. doi: 10.1155/2019/3295725. eCollection 2019.

Abstract

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.

摘要

终末期肾病 (ESRD) 患者的持续炎症是导致慢性肾脏病进展的已知原因,并且与多种风险因素相关,包括营养不良、动脉粥样硬化和心血管疾病 (CVD)。急性相蛋白 pentraxin 3 (PTX3) 已被证明具有作为局部炎症生物标志物的潜力,但它在 ESRD 中的临床应用尚不清楚。在 246 名接受透析的 ESRD 患者中评估了循环 PTX3 水平和经典炎症介质(包括临床原型 C 反应蛋白 (CRP)),并分析了它们与脂质谱、脂肪因子水平以及营养、心脏和肾脏纤维化标志物的关系。记录了下一年的死亡发生情况。与经典炎症标志物相反,PTX3 水平与营养标志物呈负相关,并且与致动脉粥样硬化脂质谱相关。发现心脏和肾脏纤维化标志物以及氧化的 LDL/LDL-C 比值是 PTX3 浓度的独立决定因素。在比较炎症介质时,在调整研究中所有标志物(除炎症标志物外)以及常见的透析混杂因素后的生存模型中,PTX3 水平的增加是透析患者全因死亡率的唯一预测因子。数据支持将 PTX3 作为比经典炎症标志物更广泛的炎症生物标志物的临床适用性,它与炎症、营养不良、CVD 和肾脏纤维化密切相关,并且具有预测透析患者全因死亡率的巨大潜力。PTX3 的多效性特征可能具有临床意义,并且可以针对它来改善与 ESRD 相关的高发病率和死亡率。

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