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Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network

机译:生物标志物研究可改善腹膜透析的临床结果:欧洲腹膜透析培训和研究(EuTRiPD)网络的共识

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摘要

Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents. Currently used biomarkers such as interleukin-6, interleukin-8, ex vivo–stimulated interleukin-6 release, cancer antigen-125, and advanced oxidation protein products that were collected through a Delphi procedure were first triaged for inclusion as surrogate endpoints in a clinical trial. Next, novel biomarkers were selected as promising candidates for proof-of-concept studies and were differentiated into inflammation signatures (including interleukin-17, M1/M2 macrophages, and regulatory T cell/T helper 17), mesothelial-to-mesenchymal transition signatures (including microRNA-21 and microRNA-31), and signatures for senescence and inadequate cellular stress responses. Finally, the need for defining pathogen-specific immune fingerprints and phenotype-associated molecular signatures utilizing effluents from the clinical cohorts of PD patients and “omics” technologies and bioinformatics-biostatistics in future joint-research efforts was expressed. Biomarker research in PD offers the potential to develop valuable tools for improving patient management. However, for all biomarkers discussed in this consensus article, the association of biological rationales with relevant clinical outcomes remains to be rigorously validated in adequately powered, prospective, independent clinical studies.
机译:腹膜透析(PD)治疗实质上需要生物标志物作为识别PD相关并发症风险最高的患者的工具,并指导可能改善单个患者临床结局的个性化干预措施。在这份共识性文章中,欧洲腹膜透析培训和研究网络(EuTRiPD)的成员回顾了PD中生物标志物研究的现状,并提出了一些与PD患者的护理有关并且可以直接从PD中获取的生物标志物。 PD废水。首先将通过Delphi程序收集的当前使用的生物标记物(例如白细胞介素6,白细胞介素8,离体刺激白细胞介素6释放,癌症抗原125和高级氧化蛋白产物)进行分类,以作为临床的替代终点试用。接下来,选择新的生物标志物作为概念验证研究的有前途的候选物,并分为炎症标志物(包括白介素17,M1 / M2巨噬细胞和调节性T细胞/ T辅助物17),间皮向间充质转变标志(包括microRNA-21和microRNA-31),以及衰老和细胞应激反应不足的特征。最后,表达了在未来的联合研究工作中,需要利用PD患者临床队列中的流出物和“组学”技术以及生物信息学-生物统计学来定义病原体特异性免疫指纹和与表型相关的分子标记。 PD中的生物标志物研究提供了开发有价值的工具以改善患者管理的潜力。但是,对于本共识性文章中讨论的所有生物标记物,生物学原理与相关临床结果的关联仍需在功能强大,前瞻性,独立的临床研究中得到严格验证。

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