Non-invasive methods for the early detection of renal allograft rejection: the role of donor-derived (circulating) cell free DNA.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Rejection of the transplant organ remains a major obstacle in organ survival. Histological evaluation of a kidney biopsy remains the gold-standard diagnostic tool in the detection of a rejection episode but is an invasive, costly and labour-intensive procedure. Therefore, there is a critical need for non-invasive detection and prediction methods. Donor-derived cell free DNA (ddccfDNA), present in the blood and urine of the recipient after transplantation, is a potential biomarker of allograft health. An increase in the ddccfDNA fraction might point to damage to the graft. In a prospective, longitudinal clinical trial with renal transplant recipients, we will investigate whether ddccfDNA can be used as a routine marker of allograft health by measuring the ddccfDNA fraction in blood and urine with a novel, cost effective and universal technique (non-invasive organ transplant test, NIOTT). Preliminary analysis from plasma samples of 28 recipients demonstrate the feasibility of the study protocol, the cfDNA extraction and the NIOTT methodology. In this project we will further optimise the NIOTT accuracy by use of donor DNA and the protocol to extract ddccfDNA from urine samples. After inclusion of all patients, we will investigate the ddccfDNA kinetics after transplantation in recipients with stable graft function and in transplant recipients with graft associated pathologies.

Keywords:KIDNEY TRANSPLANTATION

Disciplines:Immunology, Urology and nephrology

Project type:Collaboration project