*Review* **Urinary Biomarkers for Diagnosis and Prediction of Acute Kidney Allograft Rejection: A Systematic Review**

**Francesco Guzzi 1,2,\*, Luigi Cirillo 1,2, Elisa Buti 2, Francesca Becherucci 2, Carmela Errichiello 2, Rosa Maria Roperto 2, James P. Hunter <sup>3</sup> and Paola Romagnani 1,2**


Received: 29 August 2020; Accepted: 18 September 2020; Published: 19 September 2020

**Abstract:** Noninvasive tools for diagnosis or prediction of acute kidney allograft rejection have been extensively investigated in recent years. Biochemical and molecular analyses of blood and urine provide a liquid biopsy that could offer new possibilities for rejection prevention, monitoring, and therefore, treatment. Nevertheless, these tools are not yet available for routine use in clinical practice. In this systematic review, MEDLINE was searched for articles assessing urinary biomarkers for diagnosis or prediction of kidney allograft acute rejection published in the last five years (from 1 January 2015 to 31 May 2020). This review follows the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles providing targeted or unbiased urine sample analysis for the diagnosis or prediction of both acute cellular and antibody-mediated kidney allograft rejection were included, analyzed, and graded for methodological quality with a particular focus on study design and diagnostic test accuracy measures. Urinary C-X-C motif chemokine ligands were the most promising and frequently studied biomarkers. The combination of precise diagnostic reference in training sets with accurate validation in real-life cohorts provided the most relevant results and exciting groundwork for future studies.

**Keywords:** kidney transplantation; kidney graft; T-cell-mediated rejection; antibody-mediated rejection; diagnostic test accuracy
