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.

Highlights

  • The growing call for precision medicine justifies a trend shift towards the implementation of new prognostic and diagnostic biomarkers in many fields of medicine

  • We critically summarize the results of the last five years research, the latest advances, and highlight the most frequent limitations of studies assessing urinary biomarkers for the diagnosis or prediction of acute allograft rejection

  • We focused on study design, distinction between T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) setting, evaluation of confounding (e.g., delayed graft function (DGF), infections, calcineurin inhibitors nephrotoxicity), comparison with the gold standard of diagnosis, and presence of estimates of the biomarker(s) performance in validation

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Summary

Introduction

The growing call for precision medicine justifies a trend shift towards the implementation of new prognostic and diagnostic biomarkers in many fields of medicine. Progress in molecular and biomarker technology permits the possibility to tailor and customize clinical and therapeutic approaches to the specific needs of a single patient, for a variety of medical conditions. In the setting of kidney transplantation, precision medicine is rapidly moving forward, with biomarkers a significant part of this trend. Biomarkers have been studied for early recognition and diagnosis of disease recurrence, delayed graft function (DGF), infections, and acute and chronic allograft rejection [4]. Novel biomarkers could be of great help for early recognition of allograft disease, and for monitoring disease activity, optimizing the need for invasive biopsies, predicting the effectiveness and safety of a certain treatment, and tailoring the management of each single patient to their specific needs [4,8]

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