BIOMARGIN research project aims to prevent, diagnose lesions in transplanted kidneys

The BIOMARGIN (BIOMArkers of Renal Graft INjuries in kidney allograft recipients) research project, coordinated by INSERM, has just received financing from the "health" seventh framework programme of the European Commission to the tune of 6 million euros for a four-year period. The aim of the project is to develop more effective, non-invasive methods to prevent and diagnose lesions in transplanted kidneys so as to improve treatment and the long-term survival of the graft. Thirteen European research teams located in France (Inserm, AP-HP, CEA, CNRS, Université Paris Descartes, CHU de Limoges), Belgium, Germany and Sweden will work together on a so-called "omics" innovative approach involving the simultaneous study of a large number of genes, proteins and metabolites in order to identify biomarkers for these lesions on a large scale.

Patients who have received kidney transplants in the past twenty years have benefited from a significant decrease in the number of acute rejections in the first months of the transplant but graft survival beyond ten years has only improved slightly. Biopsy of the transplanted kidney remains the examination of reference for the detection of lesions in an allograft. However, this is an invasive technique whose interpretation is often difficult. "It is thus necessary to develop reliable, non-invasive methods to  diagnose allograft lesions in order to improve treatment and thus extend the long-term survival of the allograft", explains  Prof. Pierre  Marquet,  Co-ordinator of the  BIOMARGIN  European  project  and  Director  of  the UMR 850

Inserm / Université de Limoges / CHU de Limoges entitled "Pharmacology of immuno-suppressants and transplantation". This project will also make it possible to analyse the patho-physiological, immune and non-immune mechanisms involved in the long-term graft survival, at a European level.

In order to set-up these non-invasive diagnostic tools, the BIOMARGIN European project researchers chose an integrated and systematic research approach combining all the currently available "omics" technologies (identification of the expression of nucleic acids, peptides, proteins, lipids, metabolites, etc.) with analysis of blood and urine samples, as well as of graft biopsies for comparison purposes and to enable understanding of the lesion mechanisms.

The purpose of the BIOMARGIN project is to:

- Discover, select and validate biomarkers of lesions in grafted kidneys, as indicated from the blood and/or urine samples of adult and child renal transplant patients.
- Provide doctors with non-invasive and reliable diagnostic tests, as well as interpretation algorithms enabling more accurate and more predictive monitoring of transplant patients than at present.
- Avoid or reduce the use of biopsies and improve treatment, patient quality of life and graft long-term survival.
- Understand the mechanisms involved in the process by which lesions occur in the graft which, combined with mass spectrometry imaging, should provide pathologists with new molecular targets and tools for analysing renal graft biopsies.

The study will consist of four phases:

Phase 1: retrospective, case-control study of samples stored in the biobanks maintained by the partners (CHU Limoges, Necker Children's Hospital, MHH Hanover, KU Leuven), aimed at finding an extensive list of candidate biomarkers.
Phase 2: selection of biomarkers with good diagnostic performance for histological lesions in the graft.
Phase 3: validation of the diagnostic performance of biomarker candidates in a representative sample of transplant patients.
Phase 4: validation of the biomarker diagnostic and prognostic performance in newly transplanted kidney recipients recruited for the project.