Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.
Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.
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DOI：
10.1111/ajt.12426
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
CTOT-01 consortium
中科院分区：
文献类型：
--
作者：
Hricik DE;Nickerson P;Formica RN;Poggio ED;Rush D;Newell KA;Goebel J;Gibson IW;Fairchild RL;Riggs M;Spain K;Ikle D;Bridges ND;Heeger PS;CTOT-01 consortium
需要非侵入性生物标志物来评估免疫风险，并最终指导肾移植后的治疗决策。实现这些目标的一个必要步骤是验证诊断和/或预测相关移植终点的标记物。器官移植临床试验-01方案是一项对280名成人和儿童首次肾移植受者的生物标记物的多中心观察研究。我们比较和验证了尿mRNAs和蛋白作为生物标志物来诊断活检证实的急性排斥(AR)，并根据发生AR或进行性肾功能障碍的风险将患者分组。在AR的诊断指标中，尿CXCL9 m RNA[优势比(OR)2.77，阳性预测值(PPV)61.5%，阴性预测值(NPV)83%]和CXCL9蛋白(OR 3.40，PPV 67.6%，NPV 92%)最为可靠。从稳定的同种异体移植受者获得的6个月后尿液中的低尿CXCL9蛋白将最不可能发展为未来AR或估计的肾小球滤过率在6至24个月之间(92.5-99.3%的NPV)的个体分类。我们的结果支持将尿CXCL9用于肾移植后的临床决策。在急性功能障碍的情况下，较低的值可以排除损伤的感染/免疫原因。移植后6个月尿CXCL9缺失定义了早期免疫损伤风险较低的亚组。
Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5–99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.
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影响因子：
1.8
作者：
Austin, PC;Tu, JV
通讯作者：
Tu, JV
影响因子：
8.8
作者：
Hirt-Minkowski, P.;Amico, P.;Schaub, S.
通讯作者：
Schaub, S.
DOI：
10.1111/j.1600-6143.2011.03680.x
发表时间：
2011-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Jackson JA;Kim EJ;Begley B;Cheeseman J;Harden T;Perez SD;Thomas S;Warshaw B;Kirk AD
通讯作者：
Kirk AD
影响因子：
6.1
作者：
Tripepi, Giovanni;Jager, Kitty J.;Zoccali, Carmine
通讯作者：
Zoccali, Carmine
影响因子：
39.2
作者：
Levey, Andrew S.;Coresh, Josef;Van Lente, Frederick
通讯作者：
Van Lente, Frederick