Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Renal Iñigo Álvarez de Toledo, Universidad Autónoma de Madrid. REDinREN, Avda. Reyes Católicos, 2, 28040, Madrid, Spain.
Mosaiques Diagnostics GmbH, Rotenburger Str. 20, 30659, Hannover, Germany.
Sci Rep. 2018 Oct 29;8(1):15940. doi: 10.1038/s41598-018-34386-8.
Chronic kidney disease is associated with increased risk of CKD progression and death. Therapeutic approaches to limit progression are limited. Developing tools for the early identification of those individuals most likely to progress will allow enriching clinical trials in high risk early CKD patients. The CKD273 classifier is a panel of 273 urinary peptides that enables early detection of CKD and prognosis of progression. We have generated urine capillary electrophoresis-mass spectrometry-based peptidomics CKD273 subclassifiers specific for CKD stages to allow the early identification of patients at high risk of CKD progression. In the validation cohort, the CKD273 subclassifiers outperformed albuminuria and CKD273 classifier for predicting rapid loss of eGFR in individuals with baseline eGFR > 60 ml/min/1.73 m. In individuals with eGFR > 60 ml/min/1.73 m and albuminuria <30 mg/day, the CKD273 subclassifiers predicted rapid eGFR loss with AUC ranging from 0.797 (0.743-0.844) to 0.736 (0.689-0.780). The association between CKD273 subclassifiers and rapid progression remained significant after adjustment for age, sex, albuminuria, DM, baseline eGFR, and systolic blood pressure. Urinary peptidomics CKD273 subclassifiers outperformed albuminuria and CKD273 classifier for predicting the risk of rapid CKD progression in individuals with eGFR > 60 ml/min/1.73 m. These CKD273 subclassifiers represented the earliest evidence of rapidly progressive CKD in non-albuminuric individuals with preserved renal function.
慢性肾脏病与 CKD 进展和死亡风险增加有关。限制进展的治疗方法有限。开发用于早期识别最有可能进展的个体的工具将允许在高危早期 CKD 患者中丰富临床试验。CKD273 分类器是一个由 273 种尿肽组成的面板,可实现 CKD 的早期检测和进展预后。我们已经生成了基于尿液毛细管电泳-质谱的 CKD273 亚分类器,这些亚分类器针对 CKD 阶段特异性,可用于早期识别 CKD 进展风险高的患者。在验证队列中,CKD273 亚分类器在预测基线 eGFR>60ml/min/1.73m 的个体 eGFR 快速下降方面优于白蛋白尿和 CKD273 分类器。在 eGFR>60ml/min/1.73m 和白蛋白尿<30mg/天的个体中,CKD273 亚分类器预测 eGFR 快速下降的 AUC 范围为 0.797(0.743-0.844)至 0.736(0.689-0.780)。在调整年龄、性别、白蛋白尿、DM、基线 eGFR 和收缩压后,CKD273 亚分类器与快速进展之间的关联仍然显著。尿肽 CKD273 亚分类器在预测 eGFR>60ml/min/1.73m 的个体快速 CKD 进展风险方面优于白蛋白尿和 CKD273 分类器。这些 CKD273 亚分类器代表了肾功能正常的非白蛋白尿个体中快速进展性 CKD 的最早证据。