REVIEW CURRENT OPINION Innovations in kidney paired donation transplantation Thomas D’Alessandroa and Jeffrey L. Vealeb 08/05/2019 on 0Vjoh2BMKfJuUkHoodOdXjR2yjzWlLR6z+/WBPt0fgIAY/BkOPsEEse9iNcZcghkTcy8Nh3ngyORIDpHnJbSLVhRTI9Z3rxh9POLCIbTf1m7ecfbadmpPffnhj2P4cO1VIYLzOdT+5BK8rhUGKhNcSl9QmIz3s46eLHLtp148zzk3fQmpOL462dClUGp72/T by https://journals.lww.com/co-transplantation from Downloaded Downloaded from Purpose of review https://journals.lww.com/co-transplantation To analyze the innovations that have increased the reliability, convenience, and outcomes of kidney paired donation (KPD) that has led to thousands of living donor kidney transplants across the United States. Recent findings Over the past 10 years, KPD has grown over 200% on an annual basis. Though concerns had existed over cold ischemia time, research has shown that there is no correlation between travel time of a shipped kidney and the transplant outcome. The voucher program has started to continue to expand how to by 0Vjoh2BMKfJuUkHoodOdXjR2yjzWlLR6z+/WBPt0fgIAY/BkOPsEEse9iNcZcghkTcy8Nh3ngyORIDpHnJbSLVhRTI9Z3rxh9POLCIbTf1m7ecfbadmpPffnhj2P4cO1VIYLzOdT+5BK8rhUGKhNcSl9QmIz3s46eLHLtp148zzk3fQmpOL462dClUGp72/T overcome obstacles to donation by solving the issue of a pair chronological incompatibility. Summary KPD is a relatively new field and the innovations it has spawned should continue to improve availability of high-quality living donor organs. The introduction of the family voucher should continue this trend. Keywords kidney transplantation, paired exchange, transplant INTRODUCTION With research demonstrating no correlation between cold ischemic time (CIT) and graft failure By expanding the donor pool and providing incom- && patible pairs, an opportunity to receive a living [3 ], the shipping of living donor kidneys has donor kidney transplant, or enabling compatible become the standard in the United States with pairs an opportunity to receive a better match, nearly 3000 living donor kidneys traversing the kidney paired donation (KPD) is a remarkable inno- country to date [4]. vation in and of itself. As KPD becomes an increas- The increase in transporting living donor ingly common approach to kidney transplantation, kidneys via commercial airlines introduced a advancements and innovations within KPD have potential risk of losing visibility to the where- furthered that growth by more than 200% from abouts of these organs. To mitigate this risk, in 10 years ago (Fig. 1) [1]. 2010 the National Kidney Registry (NKR) began providing all donor centers with global position- ing system (GPS) devices to ship with the kidneys. SHIPPING LIVING DONOR KIDNEYS On numerous occasions, the GPS has helped to Perhaps the most significant of any advancement identify instances in which the kidney was not in KPD occurred on 30 July 2008, when a living placed on the scheduled flight. In cases like these, donor kidney was shipped across the United States the kidney can be quickly recovered and the ship- unaccompanied on a commercial airline [2]. ment expedited on a different flight to the Before this sentinel event, donors typically trav- recipient center. elled to their KPD matched recipient’s city for major surgery at an unfamiliar hospital, recover- ing apart from family and friends. The shipping of aThe National Kidney Registry, Babylon, New York and bDepartment of living donor kidneys eliminated this significant Urology, David Geffen School of Medicine at UCLA, Los Angeles, barrier to KPD participation, and resulted in a California, USA much larger pool of donor/recipient pairs. This Correspondence to Thomas D’Alessandro, National Kidney Registry, 42 on innovation drastically increased the likelihood Fire Island Avenue, Babylon, NY 11702, USA. Tel: +1 631 560 7887; 08/05/2019 of recipients finding a match, and donors no fax: +1 800 401 8919; e-mail: [email protected] longer were required to leave their preferred sur- Curr Opin Organ Transplant 2019, 24:429–433 roundings to participate in a kidney exchange. DOI:10.1097/MOT.0000000000000669 1087-2418 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-transplantation.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Kidney pancreas the NKR, there was a 27% lower 5-year graft failure KEY POINTS rate when compared to traditional directed living && KPD provides the ability for patients to be matched donor transplants (Fig. 3) [6,7 ]. NKR researchers against a larger donor pool, increasing the opportunity attribute the better KPD transplant outcomes to for kidney transplantation. superior antibody avoidance [6]. Laboratory innovations such as cryopreservation have increased the convenience for donors whereas LABORATORY improving the speed of the paired exchange process. Lab innovations have expanded outside of HLA Better outcomes of NKR paired exchange transplants, matching and into process improvement initiatives when compared to other types of living kidney for paired exchange, benefiting the transplant cen- donation, is attributed to superior antibody avoidance. ters and donors alike. Among the process innova- Vouchers take KPD one step further by resolving the tions is the use of exploratory cross matching to test problem when donor recipient pairs are incompatible for HLA compatibility in advance of initiating a by time. swap [8]. Although the use of exploratory cross matching helped a few highly sensitized patients get transplanted and reduced the rate of swap fail- ures because of unacceptable cross match results, it Consistent with a larger pool of incompatible was still difficult to obtain a fresh blood sample from donor/recipient pairs, better human leukocyte anti- a donor for what was not yet an actual match. It was gen (HLA) matches are achieved with the avoidance not until 2015 when the NKR implemented multi- of desensitization. As paired exchange volume has center donor blood cryopreservation that explor- increased, the use of desensitization has decreased atory cross matching became fully utilized and (Fig. 2) [5]. Patients with a calculated panel reactive yielded substantial results all whereas not inconve- antibodies (cPRA) lower than 99% can generally find niencing the donor. This cryopreservation innova- a clean match through the NKR in less than 6 tion enabled transplant centers to dramatically months. Patients with a cPRA greater than 99%, reduce the time to complete a cross match from who are unable to find a clean match after 6 months, 1–2 weeks to 1–2 days, facilitating more transplants often combine desensitization with KPD to reduce for highly sensitized patients and reducing swap donor-specific antibodies conflicts and achieve bet- failures caused by unacceptable cross matches. ter outcomes. In a recent report that reviewed the Donor blood cryopreservation also reduces the first 9 years of KPD transplants facilitated through number of times a donor needs to have blood drawn FIGURE 1. US paired exchange growth. 430 www.co-transplantation.com Volume 24 Number 4 August 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Kidney paired donation transplantation D’Alessandro and Veale FIGURE 2. Desensitization in National Kidney Registry (NKR) transplants. for cross matching, making paired exchange more on matching algorithms, computer software, and convenient for donors [9]. logistical optimization. In 2012, Dr. Lloyd Shapley (UCLA) and Dr. Alvin Roth (Harvard) won the Nobel MATHEMATICAL AND LOGISTICAL Prize in part for applying the ‘Gale-Shapley match- OPTIMIZATION ing algorithm’ to kidney exchanges. As KPD has The success of KPD goes beyond the surgical proce- continued to grow, more complex mathematical dure or immunosuppressive medications and hinges algorithms have been developed and real-time FIGURE 3. Transplant outcomes. 1087-2418 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-transplantation.com 431 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Kidney pancreas FIGURE 4. Voucher donation. feedback can be provided to the transplant center THE VOUCHER based on their donor’s matching potential, pref- KPD was first completed in South Korea in the form erence settings, and composition of the pool. A of two-paired exchange, also referred to as a swap, KPD pool of 100 incompatible donor/recipient [11] and later with the addition of nondirected pairs has the potential to be shuffled into trillions donors evolved into chains [12]. The next big evo- of possible chain combinations [10]. This requires lution of KPD could be the ‘voucher’ in which the implementation of powerful software systems donors donate their kidney when convenient and to perform this computation. One example of their intended recipient receives a transplant when/ logistical optimization is the development of ana- if needed [13&&]. KPD dogma initially dictated that tomical image sharing among member centers of the donor operations should occur simultaneously, the NKR. Previously, transplant coordinators were or that the paired original donor should only donate burdened by sharing the computerized tomogra- after their intended recipient (often family member) phy (CT) images of the donors’ kidney anatomy had received a kidney. However, by performing the with outside centers. Delays occurred as computer donor procedure ‘out-of-sequence’ or ‘in-advance’ disks of the images were mailed across the coun- of the intended original recipient’s transplantation try, and surgeons often had difficulty viewing the enables operating