A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation

Els M Gielis; Jacqueline D H Anholts; Els van Beelen; Geert W Haasnoot; Hans W De Fijter; Ingeborg Bajema; Sebastiaan Heidt; Mathijs van de Vrie; Luuk B Hilbrands; Marko J K Mallat; Kristien J Ledeganck; Frans H J Claas; Michael Eikmans

doi:10.1097/TXD.0000000000001169

A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation

Transplant Direct. 2021 Jun 10;7(7):e711. doi: 10.1097/TXD.0000000000001169. eCollection 2021 Jul.

Affiliations

¹ Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
² Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.
³ Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Nephology, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

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.