Degree of HLA Mismatch May Not Matter

[okarol]

Degree of HLA Mismatch May Not Matter

John Schieszer
February 23 2009

MARCO ISLAND, Fla.—The transplant community may want to rethink the importance of HLA mismatches when considering live donor kidney transplants, according to new data presented here at the American Society of Transplant Surgeons (ASTS) 9th Annual State of the Art Winter Symposium.

In the 1990s, increasing degrees of HLA mismatching correlated with a stepwise increased risk of graft loss among living donor kidney transplant recipients. With improvements in immunosuppression and patient care, however, this may no longer be the case.

“We found that the degree of HLA mismatch no longer matters,” said lead investigator Jayme Locke, MD, senior surgical resident at Johns Hopkins Medical Institutions in Baltimore. “In other words, there is no stepwise association between increasing degrees of mismatch and increasing risk for graft loss. In fact, with regard to HLA matching, the only predictor of improved graft survival is a 0 HLA mismatch.”

The new findings have implications for patients who have more than one potential living donor and for those trying to develop a matching algorithm for national kidney paired-donation (KPD) programs. If HLA mismatches are not that clinically significant, then other factors can be used to select or rule out live donors, such as comorbidities.

HLA matching still plays a role in donor selection for both living and deceased donor kidney transplantation and in some KPD program matching algorithms, Dr. Locke said. Although it is still widely accepted that HLA matching is highly relevant in predicting survival in deceased renal donor transplants, there is debate within the transplant community about the true utility of HLA matching in predicting survival in live kidney donor transplants.

Dr. Locke and her colleagues analyzed data from 76,346 adult primary live renal donor transplant recipients. They obtained 1990-2007 data from the United Network for Organ Sharing. All of the transplants were analyzed according to their degree of HLA mismatch, donor and recipient relationship (live related renal donor [LRRD] vs. live unrelated renal donor [LURD]), and by transplant era (1990-1999 vs. 2000-2007). Independent of transplant era, increasing degrees of HLA mismatch did not correlate with a stepwise reduction in graft survival after LURD transplant. In addition, 0 HLA mismatches did not confer a reduction in graft loss risk. The investigators concluded that HLA matching should be considered only when choosing among related live donors and that HLA should not be used to match the right donor to the right recipient in an incompatible KPD pool.

“When it comes to KPD programs, if you are going to award points you should award points only for someone who has a perfect match overall or at the A locus and that's it,” Dr. Locke told Renal & Urology News. “There should not be points awarded for decreasing degrees of mismatch.”

“The simpler your algorithm and the fewer things you prioritize for a match, the more weight other priorities can play,” she said. “So, instead of awarding points for each degree of mismatch, KPD algorithms should focus on more important priorities such as geography and logistics.”

http://www.renalandurologynews.com/Degree-of-HLA-Mismatch-May-Not-Matter/article/127708/

[pelagia]

But, there's one one thing I don't think they are saying.  The newer immunosuppressives do a great job of preventing rejection over 10-15 years periods, but they are also toxic to the kidney.  From what I understand, the rejection rates are holding constant, even with more mismatches.  But, at the same time, the graft survival rates aren't going up.  I have to wonder if this is somehow a byproduct of the levels of immunosuppression they need to keep those mismatched kidneys from rejecting. 

(this is when I wish Stauff was around)

[Zach]

From what I understand, the rejection rates are holding constant, even with more mismatches.  But, at the same time, the graft survival rates aren't going up.  I have to wonder if this is somehow a byproduct of the levels of immunosuppression they need to keep those mismatched kidneys from rejecting. 

Excellent point!

Another byproduct of today's level of immunosuppression may be additional side effects and co-morbidities in the long run.

[Rerun]

They call that "Job Security" - keep them coming back.