Alberta Transplant Applied Genomics Centre

MMDx-Kidney System

Investigators: Drs. Philip F Halloran, Konrad Famulski, Jeff Reeve, and the MMDx-Kidney Study Group ( NCT01299168)
Our kidney program uses microarray analysis of transcriptional changes as a tool to improve diagnosis, and to understand the pathogenesis of various human diseases including allograft rejection. A major focus has been to define the markers that differentiate T cell-mediated rejection (TCMR) from antibody mediated rejection (ABMR) - please see The ATAGC histology regression equations and Reference Standard classification for kidney transplant biopsies. This is significant because these events require different treatment strategies, resulting in different treatment responses and graft outcomes. 
Using the knowledge we generate with microarrays in concert with the clinical information and outcomes we obtain by tracking kidney transplant patients over time, we can reclassify the information in the biopsy, and improve diagnostic accuracy.  We are establishing a new diagnostic system for defining the disease states in kidney transplants in order to understand, prevent, and treat the diseases that cause graft failure - please see the Molecular Microscope® System (MMDx).
MMDx was applied to a multicentre observational clinical trial in the INTERCOM trial ( NCT01299168), where validation of the MMDx was demonstrated.
We are currently initiating a validation study combining the molecular and histological features of transplant biopsies, plus clinical and laboratory parameters, to establish the first Integrated Diagnostic System through the INTERCOMEX study.  This prospective study will include 500 unselected biopsies for clinical indications from American, Canadian and European centers.  In addition to demonstrating the feasibility and value of the MMDx in routine patient care and clinical trials, the study will develop and optimize a transparent, user-friendly reporting format to communicate this information to customers, and obtain detailed feedback from clinicians caring for the study patients.  The INTERCOMEX project will further clinical relevance of this technology by providing 24 hour turn-around time, measuring response to therapy and providing an integrated report for each biopsy. The results will impact patient management and the design of clinical trials for development of new drugs. Moreover, the kidney transplant MMDx system is the prototype for other organ transplants and primary organ diseases, and a Rosetta stone for reclassifying many disease states.