Hot topics in kidney transplantation by Dr. Dorry Segev – Paradigm 5: Kidney exchange beyond incompatibilities

According to the old paradigm, it was believed that kidney exchange only benefits ABO/HLA-incompatible pairs. This was a major limitation in itself. Today we recognize that exchange goes well beyond ABO/HLA incompatibilities. Currently, we can quantify the quality of the donor by estimating the KDPI of the kidneys. When compatible pairs participate in kidney exchange programs, it allows more incompatible recipients to find a match. In a group of people who are ABO compatible, it’s more likely that one can find a blood type O donor. O donors bring a diverse distribution of blood types and more common HLAs into the population. They allow more incompatible pairs to match by bringing a different phenotype into the pool, thereby allowing others to benefit as well. 

It has been noted that eplet matching is the most recent attempt to employ kidney exchange to improve donor facilitation. If we can better understand what causes immunologic injury, such as de novo donor-specific antibodies (dnDSA) development and subclinical rejection, then it may be possible to provide kidneys that can live longer. This also suggests that patients who stand to benefit from it might have to take fewer immunosuppressants. This enables it to be more robust to noncompliance, which is frequently encountered. We now understand that eplets, as opposed to HLA antigens, which are more frequently utilised, may be a better method for estimating immunologic risks. An eplet is an immunologic hotspot on an HLA antigen. These eplets are then used to analyse the amino acid sequences and identify conserved HLAs, which can then be used to identify compatibility. 

Hence, as per the old compatibility paradigm, the compatibility was checked by examining the blood type and HLA. If they were incompatible, the donor kidneys would have been excluded to find another suitable donor by exchange or desensitization would've been carried out. The living kidney donor transplant would only be performed if ABO and HLA were compatible.
Under the current paradigm, all of the incompatibilities are compared and identified in the process of assessment, such as HLA, pre-formed antibody, eplet mismatches, ABO, donor-recipient age nephron mismatches, etc., to improve the donor regardless of the source of incompatibilities.