$0 Raised

Brendan Keating

Associate Professor, Division of Transplantation, Department of Surgery and Pediatrics
University of Pennsylvania and Children's Hospital of Philadelphia

I am one of the founders of the iGeneTRAiN consortium, and a principal investigator on a number of urinary biomarker studies for adult and pediatric kidney transplant clinical studies. I am also heavily involved in liver and heart transplant clinical studies to validate biomarkers of post-transplant complications such as acute rejection. As a geneticist, I am highly motivated by the knowledge that we now have the genomic tools to interrogate the biospecimens of transplant recipients to assess the status of their transplanted organ.

Summary

One of the most common complications after a kidney transplant is acute rejection, which significantly increases the likelihood of organ-failure and patient death. The current standard for determining rejection is through highly-invasive and costly needle biopsies of the transplanted organ. One of the main issues here is that rejection, and subsequent organ damage has often already occurred. Our approach to detect subclinical rejection in the kidney (through urinary markers), liver (through blood markers) and in the heart (through biopsy markers) using molecular assays that may lead to major healthcare improvements for a transplant patient.

We have already developed and published prognostic and diagnostic biomarkers of acute cellular rejection in some of the largest US clinical studies ever performed in transplantation. Our project aims to solve the problem of transplant rejection monitoring by taking these findings and validating them further in additional studies.

To date, we have recruited almost 300 pediatric kidney transplant patients from 12 sites in North America (https://clinicaltrials.gov/ct2/show/NCT03719339) and have another 150 patients to go.

We are also expanding recruitment across international transplant sites for additional kidney and liver transplant patients. The consortium already includes genetic studies from >30 international partners (www.igenetrain.org). We are also combining deep genetic scans across the genomes of the transplant recipient and donors to discover the actual genetic variants that are precipitating rejection episodes.

Why is this important?

In the US alone, less than 30% of the 120,000+ patients on an organ waiting list receive a transplant. Of these, over 20% will require a re-transplant due to rejection or related complications. In the case of acute kidney rejection - a single rejection episode can shorten the lifetime of the graft by 4 years. Our solution, through the continued acquisition, collation, and analysis of urinary and blood-based biomarkers, will ameliorate the risk of rejection by accurately and predictively assessing organ health over time in a low-cost and minimally invasive manner. Our assembled consortium (www.igenetrain.org) is the only large transplant genomic transplant effort to date (with deep genetic data generated on >56,000 subjects).

Who will benefit?

This will benefit transplant recipients, their families, and their providers. Further, we are confident that the direct benefits of an extended lifetime of the transplanted organ will greatly benefit those on the waiting list by freeing up organs as the number of re-transplants will be reduced. The costs of an individual going back on dialysis is $70,000 to $80,000 per year, and re-transplantation has significant cost and health risks.