Science Translational Medicine: A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection

Science Translational Medicine

Mar 18, 2020

Joshua Y. C. Yang, Reuben D. Sarwal, Tara K. Sigdel, Izabella Damm, Ben Rosenbaum, Juliane M. Liberto, Chitranon Chan-On, José M. Arreola-Guerra, Josefina Alberu, Flavio Vincenti, and Minnie M. Sarwal

Transplant monitoring via urine

For kidney transplant recipients, prompt and accurate detection of transplant rejection is vital for timely intervention. Unfortunately, the gold standard for diagnosis of rejection is kidney biopsy, an invasive procedure. Moreover, the presence of pathological rejection does not always correlate with symptoms or laboratory values, so even clinically stable patients have to be subjected to periodic biopsies. To facilitate the monitoring of kidney transplant patients, Yang et al. adapted a urine biomarker assay similar to one previously tested for the detection of chronic kidney disease. The noninvasive urine assay showed strong performance in multiple cohorts of patients, suggesting its potential for clinical translation.

Abstract

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.

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