The EUropean TRAnsplantation and INnovation Consortium for Risk Stratification in Kidney Transplant Patients

Allograft rejection is still a major threat to allografts with thousands of allografts failing every year worldwide due to organ rejection, with immediate consequences for the patients in terms of mortality and morbidity. With a prevalence around 20% in the first-year post transplant, rejection also carries high economic impact representing a 72% increase in transplantation price and downstream cost because of return on dialysis (60,000€ health care increase per patient). The rough estimates from 200,000 kidney allograft failures per year equals to 12 billion extra cost for the health care system per year.

Various explanations may be involved: 1) The current stratification system relies on various elements of the follow up of standard of care after kidney transplantation (histology, immunology) taken separately and, 2) Current therapeutic strategy is a "one fit for all" approach. Literature data show that therapeutics are not individualized, with 98% of patients having the same immunosuppressive regimens without analysis of response to therapy; 3) Lack of integration of omics in the stratification process. Today, the only approaches used to monitor the advent of immune-mediated allograft damage are nonspecific markers such as serum creatinine level and proteinuria which are not integrated in a dynamic approach. Some kidney transplant programs have implemented surveillance allograft biopsies, but they lack specificity and sensitivity and do not provide etiopathology of the underlying process. This impairs the risk stratification process.

In this project, leading European scientific teams, which have created relevant population cohorts and expertise, have joined forces to allow for large-scale (>5,000 patients) risk prediction studies in the field of kidney transplantation. The overall goal of the EUropean TRAnsplantation and INnovation consortium (EU-TRAIN) is to prevent kidney allograft failure and improve allograft survival by informing clinical decision and delivering optimised interventions to patients at individual level. The project aims to improve the current gold standard for risk stratification and prognosis among kidney transplant recipients.

The members of the EU-TRAIN consortium have invested heavily in the last decade to create large highly detailed European kidney transplant cohorts and to achieve best level scientific expertise in the assessment of innovative biomarkers and rejection reclassification on the basis of disease mechanism using gene expression. Ground-breaking concrete results have already been obtained that have changed patient care and transplant medicine guidelines: This is underlined by highly cited publications in the leading specialised journals and also in journals aimed at a popular audience that underlines the systemic nature of this approach, (NEJM (n=10), Lancet (n=2), BMJ (n=1), JASN (n=18)). Using this approach, the investigators have recently identified new forms of allograft rejection, resulting in changes in the most recent international allograft Banff classification and reclassifying rejection diagnosis and disease stage. This research strategy also led to recently demonstrate the clinical relevance of new non-invasive biomarkers for defining the pathogenicity of anti-HLA antibodies and allograft loss risk assessment and incorporate gene expression measurements in allograft rejection risk stratification.

The EU-TRAIN project will further elevate these cohorts synergistically by adding data on novel biomarkers, so far underdeveloped in kidney transplant research, in particular genomics and immunological data. A comprehensive integration strategy of these exceptionally large and complete cohorts constitutes a quantum leap in transplant research, and offers a unique opportunity, out of reach so far, to design strategies for truly personalised medicine.