RD Néphrologie, Montpellier, France.
PLoS One. 2013 May 14;8(5):e62837. doi: 10.1371/journal.pone.0062837. Print 2013.
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.
国家肾脏基金会的 CKD 分期方法使 CKD 的研究实现了标准化。然而，在早期诊断和预测终末期肾病进展方面，还有待进一步改善。本研究对 76 例不同 CKD 程度的患者（包括门诊患者和透析患者）进行了转录组、代谢组和蛋白质组学描述。对 76 例 CKD 患者中的 53 例非无尿患者进行了高分辨率尿蛋白质组分析。除了常规临床参数外，还对基于尿液蛋白质组学的分类器 CKD273 及其肽进行了定量分析。对基线值进行了分析，以评估其与临床参数的相关性，并以随访（3.6 年）期间死亡或肾脏死亡的发生作为主要结局测量。在 CKD273<0.55 的患者中，没有一个需要透析或死亡，而所有达到终点的 15 名患者的 CKD273 评分均>0.55。未对 CKD273 肽进行无监督聚类分析，将患者分为两个主要组，两组之间的 CKD 相关参数存在差异。在 273 个生物标志物中，肾小球滤过率较低的患者中来源于血清蛋白的肽相对增加，而来源于胶原蛋白的肽相对减少（p<0.05；Spearman）。不同肾功能组之间 CKD273 不同（p<0.003）。CKD273 分类器根据患者的肾功能对 CKD 患者进行了分类，并告知了其发生不良结局的可能性。最近在一项大人群研究中定义的 CKD273 是第一个成功用于独立队列 CKD 进展预后预测的基于蛋白质组学的分类器。
