World repercussion of the NEJM desensitization article – A Brazilian perspective

The recently published paper in the NEJM entitled “Survival Benefit with Kidney Transplants from HLA-Incompatible LiveDonors” caused a huge impact on Brazil’s media. Our main broadcast TV devoted few minutes explaining it, suggesting as a real breakthrough. Patients and many members of our multidisciplinary team were questioning if compatibility could be forgotten as a barrier to transplantation.

         Moved by this repercussion, on our weekly meeting we debated the article. Three questions were posed:

       1. Does transplanting HLAi patients really improve quality of life (life expectancy was shown to be expanded), compared to waiting on the list for a deceased donor?

       2. Why 5-year life expectancy for live donor kidney recipients in the US is 86% (USRDS data), while in the UK, Australia and at our own service it is around 97%. Does anyone has any suggestion of why such a huge difference?

       3. What about the high costs of desensitization? 

The former question is far from our reality. In our center, we do not perform HLAi transplants despite our high volume of over 900 kidney transplants per year. Due to low reimbursement, complications that may arise from HLAi transplants such as re-hospitalizations, requirement for additional plasmapheresis and IVIG as well as biopsies may significantly affect the cost of post-transplant care and prevent appropriate treatment of complications.

This cautious approach to cost is immensely influenced by our political and economical scenario. After chaotic administration and corruption, our GPD is falling ~3%. State health insurance is paying less than the actual cost for a dialysis session. In some centers, this is forcing doctors do reduce the dialysis session by 30 minutes (from 240 minutes to 210 minutes/session). In this context, proposing a new and costly treatment (like desensitization) that should be reimbursed by our Public Health System would sound as an outrage to the state health managers. Clearly, it seems the media has been over optimistic with the article conclusions. Many centers in the USA are actually favoring kidney paired exchange to minimize the complications and costs of desensitization. What do physicians from developing countries think about this? Additional comments are appreciated. 

Thiago Reis, MD

Hospital do Rim, UNIFESP, São Paulo, Brazil 

Is Matching at the HLA Epitope Level the Holy Grail of Longer Graft Survival?

All HLA antigens are composed of strings of several polymorphic sites, which may serve as targets, or epitopes, for antibody binding. An important consideration is that HLA antigens have multiple epitopes that can be recognized by specific antibodies. The current nomenclature of the HLA system does not take into account the nature or identity of these epitopes. Elucidation of three-dimensional molecular structures and amino acid sequence differences between HLA antigens has made it possible to define the structural basis of HLA epitopes (reviewed by Tambur, Claas AJT 2015).

Why could this be important?
For certain HLA phenotypes a given mismatch has no or few mismatched epitopes and for other phenotypes, the same HLA antigen has many mismatched epitopes and is therefore, structurally highly incompatible. Altogether, the degree of structural compatibility of a donor HLA mismatch is largely determined by the HLA type of the recipient. Therefore, the level of epitope match may help identifying the best compatible donor. Furthermore, it may identify epitopes that are most immunogenic and lead to a greater risk of antibody generation post-transplant (Wiebe et al. AJT 2013).

How can you do this?
HLA Matchmaker, a computer algorithm available for free at www.hlamatchmaker.net, determines histocompatibility at the epitope rather than antigen level. Therefore, it can provide an estimate of the degree of epitope matching or mismatching.

Who would benefit the most?
Highly sensitized patients with difficult matches and younger patients to minimize risk of de novo DSA development post-transplant.