Impact of blood products on renal transplant allosensitisation

Abstract

Patients with end stage renal disease (ESRD) who are sensitised with anti-human leucocyte antibodies (HLA) spend a longer time on the transplant wait list and have a greater risk of morbidity and mortality. Post-transplantation, sensitisation is significantly associated with inferior allograft outcomes, with chronic antibody medicated rejection (AMR), the leading cause of failure. Efforts to prevent sensitisation is key, as a unified approach to AMR management is lacking and desensitisation is not without risk.

Blood transfusions, pregnancy and previous solid organ transplantation all increase the risk of sensitisation. Transfusions remain an important modifiable factor.

Patients transplanted at Imperial College Renal and Transplant Centre were included. Healthy blood donors, who had historically donated, were recruited via NHS Blood and Transplant. The hypothesis, transfusions are a primary sensitising event associated with inferior allograft outcomes, is addressed in the following studies: 1. What are the factors and significance of de novo non-donor specific antibodies (NDSA)? 2. Are post-transplant blood transfusions (PTBT) associated with inferior allograft outcomes? 3. Does the blood donor HLA type increase the risk of de novo donor specific antibodies (DSA) in transplant recipients that have received a transfusion? 4. Do components carry the same sensitisation risk? 5. What is the understanding of transfusions within UK transplant centres and does this reflect practice? Outcome Summary: 1. De novo NDSA are seen in males and parous females with PTBT and associated with inferior allograft outcomes. 2. PTBTs are common and independently associated with allograft loss and de novo DSA. 3. Transplant recipients produce a primary alloimmune response against the blood donor. Multiple transfusions and HLA blood donor-recipient mismatch increase alloantibody formation. 4. Platelet-only transfusions are rare and not independently associated with inferior outcomes. 5. UK adult transplant units underestimate the number of transplant patients they transfuse. Post-transplant anaemia management lacks a unified approach.