CKD273, a new proteomics classifier assessing CKD and its prognosis.

CKD273, a new proteomics classifier assessing CKD and its prognosis.
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DOI:
10.1371/journal.pone.0062837
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Mischak H
Mischak H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Argilés Á;Siwy J;Duranton F;Gayrard N;Dakna M;Lundin U;Osaba L;Delles C;Mourad G;Weinberger KM;Mischak H

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国家肾脏基金会CKD分期允许CKD研究的一致性。然而,早期诊断和预测进展到终末期肾脏疾病尚未得到改善。对76例不同程度CKD患者(包括门诊患者和透析患者)进行转录组、代谢组和蛋白质组描述研究。对76例CKD患者中的53例非尿尿患者进行了高分辨率尿蛋白质组分析。除常规临床参数外,对CKD273(一种基于尿蛋白组学的分类器)及其多肽进行定量分析。基线值以临床参数和随访(3.6年)期间死亡或肾性死亡的发生率为主要指标进行分析。没有CKD273<0.55的患者需要透析或死亡,而所有15名达到终点的患者CKD273评分为>.55。CKD273肽的无监督聚类分析将患者分为CKD相关参数不同的两组。在273个生物标志物中,肾小球滤过率较低的患者血清蛋白来源的肽相对增加,胶原来源的肽相对减少(p<0.05; Spearman)。CKD273在不同肾功能组间差异有统计学意义(p<0.003)。CKD273分类器根据肾功能对CKD患者进行分类,并告知发生不良结果的可能性。最近在大量人群中定义的CKD273是第一个基于蛋白质组学的分类器,在一个独立的队列中成功测试了CKD进展的预后。
National Kidney Foundation CKD staging has allowed uniformity in studies on CKD. However, early diagnosis and predicting progression to end stage renal disease are yet to be improved. Seventy six patients with different levels of CKD, including outpatients and dialysed patients were studied for transcriptome, metabolome and proteome description. High resolution urinary proteome analysis was blindly performed in the 53 non-anuric out of the 76 CKD patients. In addition to routine clinical parameters, CKD273, a urinary proteomics-based classifier and its peptides were quantified. The baseline values were analyzed with regard to the clinical parameters and the occurrence of death or renal death during follow-up (3.6 years) as the main outcome measurements. None of the patients with CKD273<0.55 required dialysis or died while all fifteen patients that reached an endpoint had a CKD273 score >0.55. Unsupervised clustering analysis of the CKD273 peptides separated the patients into two main groups differing in CKD associated parameters. Among the 273 biomarkers, peptides derived from serum proteins were relatively increased in patients with lower glomerular filtration rate, while collagen-derived peptides were relatively decreased (p<0.05; Spearman). CKD273 was different in the groups with different renal function (p<0.003). The CKD273 classifier separated CKD patients according to their renal function and informed on the likelihood of experiencing adverse outcome. Recently defined in a large population, CKD273 is the first proteomic-based classifier successfully tested for prognosis of CKD progression in an independent cohort.
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