1] Clinical and Biomedical Proteomics Group, Cancer Research UK Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK [2] Department of Renal Medicine, Lincoln Wing, St James's University Hospital, Leeds, UK.
Kidney Int. 2013 Dec;84(6):1214-25. doi: 10.1038/ki.2013.200. Epub 2013 Jun 5.
Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67-0.85) for ACY-1, 0.9 (0.84-0.95) for cystatin C, and 0.93 (0.88-0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor-brain-dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation.
早期识别和预后分层肾移植后延迟移植物功能障碍具有显著改善结果的潜力。对 5 例延迟移植物功能障碍患者和 5 例无并发症移植患者移植前和移植后第 2 天的血清样本进行质谱分析,鉴定出天冬氨酸酰基转移酶-1(ACY-1)作为一种潜在的预后生物标志物。在开发检测方法后,对 55 例初始验证队列患者的纵向样本进行分析,证实第 1 天或第 2 天的 ACY-1 水平是延迟移植物功能障碍的中度预测指标,与血清肌酐相似,与最强的预测标志物胱抑素 C 相辅相成。对 194 例患者的进一步验证队列证实了这种关联,第 1 天血清的 ROC 曲线下面积(95%CI)为 0.74(0.67-0.85),ACY-1 为 0.9(0.84-0.95),胱抑素 C 为 0.93(0.88-0.97)。延迟、缓慢和即刻移植物功能之间的血清 ACY-1 水平差异明显。对 54 例延迟移植物功能障碍患者的长期随访分析显示,第 1 天或第 3 天血清 ACY-1 与无透析生存之间存在高度显著关联,主要与供体脑死亡移植类型有关。因此,蛋白质组学分析为移植后立即检测血清 ACY-1 水平的潜在临床应用提供了新的见解,能够根据长期结果对延迟移植物功能障碍患者进行细分。我们的研究需要独立确认。