Antibody-mediated Rejection - an Ounce of Prevention is Worth a Pound of Cure

07:55: Giving the Incompatible Patient Hope with Kidney Paired Donation

Adam Bingaman, Texas Transplant Institute, San Antonio, USA

Live donor transplantation has emerged as a favored option for end-stage renal disease patients with willing, healthy donors since recipients can avoid long wait times on the deceased donor list and outcomes from live donor transplantation are significantly better compared to deceased donor transplantation. A significant barrier for many patients to receive a live donor kidney transplant is that they must be immunologically compatible with their donor. Desensitization and kidney-paired donation (KPD) to achieve a compatible transplant are options for patients with incompatible donors. However, desensitization techniques are expensive, may be associated with higher patient morbidity, and long-term outcomes are inferior, making KPD a preferred option. While the number of KPD transplants has been slowly increasing over the past decade, computer modeling suggests that this modality is significantly underutilized.

There has been no universal approach to the entrance of patients into KPD programs. Many transplant centers have elected to enter incompatible donor/recipient pairs into regional databases managed by KPD networks or alliances. In the United States, UNOS has recently initiated a proposal to administer an optional national program to manage KPD. The effectiveness and efficiency of single-center programs, regional KPD programs or a national program to significantly expand KPD transplants remain unknown.

KPD options include:
1. Exchange with incompatible pairs without the need for desensitization;Exchange with incompatible pairs combined with desensitization for weak incompatibility;
2. Exchange with a mix of compatible and incompatible pairs;
3. Use of non-directed donors to begin “chains”.

Effective utilization of each of these options can maximize KPD transplants for patients with incompatible donors.

Our center established a KPD program enrolling all consenting recipient candidates with incompatible donors, as well as compatible pairs with older donors and performed the first KPD transplants in March 2008. In 26 months, our center did 83 KPD transplants, including 22 two-way and 13 three-way exchanges. Non-directed donors were not used. The median time from listing in the KPD database to transplantation was 5.5 months. All recipients had negative flow crossmatches at the time of transplant and 3 required desensitization for very minor incompatibilities. Of the incompatible patients transplanted, 64% were crossmatch incompatible and 36% were blood-type incompatible with their original donors. Of the crossmatch incompatible patients transplanted, 36% had a panel reactive antibody >80%. With a median follow-up of 6 months post-transplant, there were no episodes of cellular rejection and one mild antibody-mediated rejection which was easily reversed.

KPD at a single center can increase access to live-donor transplantation with excellent outcomes. If the productivity of our single-center KPD program could be replicated on a national level in the U.S., it would result in approximately 2,000 additional live-donor transplants annually and reduce the number of patients on the waiting list. Difficult desensitization therapies could also be avoided. All transplant centers should provide access to an effective KPD program in order to give patients with incompatible donors a full range of options to achieve a successful transplant, particularly prior to desensitization attempts.

Adam Bingaman

Dr. Bingaman completed his general surgery training at Emory University in Atlanta, Georgia. During his residency he earned a Ph.D. in immunology under the direction of Dr. Chris Larsen. He completed his fellowship training in kidney and pancreas transplantation surgery at the University of Maryland. He is currently Director of the live donor and incompatible kidney transplant programs at Methodist Specialty and Transplant Hospital in San Antonio, Texas, home of the largest live donor kidney transplant program in the United States in 2009. Dr. Bingaman is board certified by the American Board of Surgery, is a member of the American College of Surgeons, and has published extensively in the field of transplantation immunology.