Developing Renal Allograft Surveillance Strategies – Urinary Biomarkers of Cellular Rejection

Abstract

Purpose of review: Developing tailored immunosuppression regimens requires sensitive, non-invasive tools for serial post-transplant surveillance as the current clinical standards with serum creatinine and proteinuria are ineffective at detecting subclinical rejection. The purpose of this review is: (i) to illustrate the rationale for allograft immune monitoring, (ii) to discuss key steps to bring a biomarker from bench-to-bedside, and (iii) to present an overview of promising biomarkers for cellular rejection. Sources of information: PubMed. Findings: Recent multicentre prospective observational cohort studies have significantly advanced biomarker development by allowing for the adequately powered evaluation of multiple biomarkers capable of detecting allograft rejection. These studies demonstrate that urinary CXCR3 chemokines (i.e. CXCL9 and CXCL10) are amongst the most promising for detecting subclinical inflammation; increasing up to 30 days prior to biopsy-proven acute rejection; decreasing in response to anti-rejection therapy; and having prognostic significance for the subsequent development of allograft dysfunction. Urinary CXCR3 chemokines are measured by simple and cost-effective ELISA methodology, which can readily be implemented in clinical labs. Limitations: Many biomarker studies are performed in highly selected patient groups and lack surveillance biopsies to accurately classify healthy transplants. Few validation studies have been done in unselected, consecutive patient populations to characterize population-based diagnostic performance. Implications: Based on these data, prospective interventional trials should be undertaken to determine if chemokine-based post-transplant monitoring strategies can improve long-term renal allograft outcomes. This last step will be necessary to move novel biomarkers from the bench-to-bedside.