Mechanistic Evaluation of Treatments for Acute Antibody-Mediated Rejection of the Kidney Transplant

The best treatment for kidney failure is a kidney transplant, but a transplanted kidney only works for about 10 to 15 years on average. One of the reasons that a transplanted kidney can stop working is that the body develops antibodies against it. Antibodies are proteins produced by the body to fight infections. They play a vital role in dealing with infection but in some transplant patients they can 'fight' the organ, meaning it could stop working. This is called acute antibody-mediated rejection (AAMR). A patient experiencing AAMR can be treated to extend the life of the transplanted kidney, but the chances of the kidney still working 4 years later are reduced. There is currently a clinical trial for UK kidney transplant patients who develop AAMR, called TAR:GET-1. Patients participating in TAR:GET-1 will either receive the standard treatment that is currently given in this situation, or the standard treatment with the addition of rituximab. TAR:GET-1 will answer the question: does adding rituximab to standard treatment lengthen the life of a kidney transplant? A second, sub-study is being proposed of the patients enrolled in TAR:GET-1, that will use the existing blood and biopsy samples already taken during TAR:GET-1 plus an optional extra biopsy of the kidney transplant, to improve our understanding of how the treatments of AAMR work. Patients enrolled in TAR:GET-1 will have had a blood test and biopsy of the transplanted kidney to establish the diagnosis of AAMR. They will also have had further blood tests after treatment, and may also have further biopsies taken if their clinician needs these as part of normal care. Material left over in these samples can be used to analyse how treatment works. In addition, patients will be asked if they agree to an extra biopsy of the transplanted kidney 6 months after the treatment begins. These samples will be analysed at a deeper level than would normally be done, looking at the antibodies and biopsies in detail to answer 2 key questions: 1) Can the unique characteristics noted in an individual patient's antibodies and biopsy predict whether a kidney transplant will be lost as a result of AAMR?; 2) Can we tell treatment is working by looking at the changes in a patient's antibodies and biopsies before and after treatment? The answers to these questions will help us understand AAMR and how its treatments work, and potentially improve our ability to select the right treatment for the right patients.