1. A combined microRNA and chemokine profile in urine to identify rejection after kidney transplantation
- Author
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Luuk B. Hilbrands, Michael Eikmans, Els van Beelen, Sebastiaan Heidt, Kristien J. Ledeganck, Mathijs van de Vrie, Geert W. Haasnoot, Marko J.K. Mallat, Jacqueline D.H. Anholts, Hans W. de Fijter, Frans H.J. Claas, Ingeborg M. Bajema, and E. Gielis
- Subjects
medicine.medical_specialty ,RD1-811 ,Urinary system ,Urology ,Urine ,030230 surgery ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,Biopsy ,medicine ,Kidney transplantation ,Transplantation ,medicine.diagnostic_test ,business.industry ,Area under the curve ,medicine.disease ,Kidney Transplantation ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Chemokine Profile ,Surgery ,030211 gastroenterology & hepatology ,Human medicine ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business ,Kidney transplant rejection - Abstract
Supplemental Digital Content is available in the text., Background. There is an unmet need for noninvasive tools for diagnosis of rejection after kidney transplantation. The aim of this study was to determine the discriminative value of a combined cellular and molecular biomarker platform in urine for the detection of rejection. Methods. First, microRNA (miR) molecules were screened in transplant biopsies and urine sediments of patients with acute rejection and patients without rejection and stable graft function. Second, the expression of 15 selected miRs was quantified in an independent set of 115 urine sediments of patients with rejection and 55 urine sediments of patients without histological signs of rejection on protocol biopsy. Additionally, CXCL-9 and CXCL-10 protein levels were quantified in the urine supernatant. Results. Levels of miR-155-5p (5.7-fold), miR-126-3p (4.2-fold), miR-21-5p (3.7-fold), miR-25-3p (2.5-fold), and miR-615-3p (0.4-fold) were significantly different between rejection and no-rejection urine sediments. CXCL-9 and CXCL-10 levels were significantly elevated in urine from recipients with rejection. In a multivariable model (sensitivity: 89.1%, specificity: 75.6%, area under the curve: 0.94, P < 0.001), miR-155-5p, miR-615-3p, and CXCL-9 levels were independent predictors of rejection. Stratified 10-fold cross validation of the model resulted in an area under the curve of 0.92. Conclusions. A combined urinary microRNA and chemokine profile discriminates kidney transplant rejection from stable graft conditions.
- Published
- 2021