Sigdel Tara K, Schroeder Andrew W, Yang Joshua Y C, Sarwal Reuben D, Liberto Juliane M, Sarwal Minnie M
Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
J Clin Med. 2020 Jul 22;9(8):2341. doi: 10.3390/jcm9082341.
Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography-mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could differentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.
尽管手术工具和治疗方法有了新进展，但接触与非免疫和免疫损伤相关的免疫抑制药物会导致器官移植缓慢恶化和过早衰竭。通过非侵入性尿液监测诊断这些损伤对于患者管理而言将是一项重大的临床进展，尤其是在儿科患者群体中。我们使用气相色谱 - 质谱联用仪（GC-MS）研究了310名独特肾移植受者活检匹配尿液样本的代谢组学谱。确定了重点代谢物组，其可检测活检确诊的急性排斥反应，灵敏度为92.9%，特异性为96.3%（11种代谢物），并且能够以88.9%的灵敏度和94.8%的特异性（4种代谢物）区分BK病毒性肾炎（BKVN）与急性排斥反应。总体而言，对活检匹配尿液样本进行靶向代谢组学分析能够生成精确的代谢物组，从而以高可信度非侵入性地检测移植物损伤表型。这些尿液生物标志物可快速评估，用于特定移植损伤的非侵入性诊断，为精准移植医学打开了窗口。
