Transplantation of the broadly sensitized patient: what are the options?

Recipient sensitization to a wide variety of human leukocyte antigens (HLA) represents a major barrier to transplantation. We discuss the options for the challenging group of broadly sensitized kidney transplant candidates.

Transplantation by way of kidney-paired donation (KPD) represents a preferable way to bypass immunological barriers. Recent data suggest that KPD programs can be optimized by the use of innovative serological techniques to define unacceptable HLA antigens, inclusion of altruistic donors or altruistic balanced paired kidney exchange, and complementary recipient desensitization. It has become evident that plasmapheresis and/or intravenous immunoglobulin (IVIG)-based crossmatch conversion may not completely prevent rejection and chronic injury. However, recent evidence suggests major improvements by sophisticated serological risk stratification and new innovative treatment principles. Wait-listed broadly sensitized patients were shown to benefit from specific allocation programs, such as priority allocation of organs via the Eurotransplant acceptable mismatch program. Recent studies have suggested a benefit from IVIG/rituximab-based desensitization on the waitlist, or apheresis-based protocols for rapid antibody removal immediately before transplantation.

A multifaceted repertoire of complementary strategies was shown to facilitate successful live and deceased donor kidney transplantation in high-risk patients. Recent promising developments can be expected to significantly improve outcomes.