Yang Joshua Y C, Sarwal Reuben D, Sigdel Tara K, Damm Izabella, Rosenbaum Ben, Liberto Juliane M, Chan-On Chitranon, Arreola-Guerra José M, Alberu Josefina, Vincenti Flavio, Sarwal Minnie M
Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Surgery, University of Mexico, Instituto Nacional de Ciencias Medicas y Nutricion, Ciudad de México, CDMX 14080, Mexico.
Sci Transl Med. 2020 Mar 18;12(535). doi: 10.1126/scitranslmed.aba2501.
Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection of acute rejection (AR) and to affect the long-term survival of the transplant. We present the development and validation of a noninvasive, spot urine-based diagnostic assay based on measurements of six urinary DNA, protein, and metabolic biomarkers. The performance of this assay for detecting kidney injury in both native kidneys and renal allografts is presented on a cohort of 601 distinct urine samples. The urinary composite score enables diagnosis of AR, with a receiver-operator characteristic curve area under the curve of 0.99 and an accuracy of 96%. In addition, we demonstrate the clinical utility of this assay for predicting AR before a rise in the serum creatinine, enabling earlier detection of rejection than currently possible by standard of care tests. This noninvasive, sensitive, and quantitative approach is a robust and informative method for the rapid and routine monitoring of renal allografts.
准确且无创地监测肾移植后的同种异体肾对于早期检测急性排斥反应(AR)以及影响移植的长期存活至关重要。我们展示了一种基于测量六种尿液DNA、蛋白质和代谢生物标志物的无创、即时尿液诊断检测方法的开发与验证。该检测方法在检测天然肾脏和同种异体肾中的肾损伤方面的性能,在一组601个不同尿液样本中得到了呈现。尿液综合评分能够诊断AR,其受试者工作特征曲线下面积为0.99,准确率为96%。此外,我们证明了该检测方法在血清肌酐升高之前预测AR的临床实用性,能够比目前的标准护理检测更早地检测到排斥反应。这种无创、灵敏且定量的方法是一种用于快速且常规监测同种异体肾的强大且信息丰富的方法。