Balancing immunogenicity and histocompatibility in kidney transplantation

Abstract

Kidney transplantation is the optimal treatment for kidney failure; however, long waiting times due to organ shortages remain a significant issue. Expanding the donor pool with organs from older donors or so-called "extended criteria donors" (ECD) is a possible solution, though this may be associated with increased complications. This thesis outlines several strategies to mitigate these risks.

Firstly, the allocation strategy, particularly in older patients, can be refined. ECD kidneys are more susceptible to rejection due to various factors, while older recipients are more vulnerable to infections, especially with the use of immunosuppressants. Improved HLA matching could reduce the risk of rejection and prospective HLA-DR matching within the Eurotransplant Senior Program provided a clear benefit. Furthermore, by focusing on amino acid-level differences rather than allele-level, the risk of anti-HLA donor specific antibody formation could be more accurately predicted.

Another promising approach regarding tolerance in kidney transplantation is the use of mesenchymal stromal cells (MSC). This dissertation introduces a study using allogeneic MSC, which was found to be safe and did not trigger antibody formation. Additionally, an innovative technique measured circulating free DNA from these MSC, revealing an early increase after administration, providing insights into the potential mechanisms of action.