Innovations in Kidney Paired Donation

Department of b www.co-transplantation.com 2019, 24:429–433 b The increase in transporting living donor ], the shipping of living donor kidneys has && The National Kidney Registry, Babylon, New York and a become the standardnearly in 3000 the livingcountry donor United to kidneys date States [4]. traversing with the kidneys viapotential commercial risk airlines ofabouts of losing introduced these visibility2010 organs. a to the To the National mitigateproviding Kidney where- all this Registry donor risk, centers (NKR)ing in system with began (GPS) global devices position- toOn ship with numerous the occasions, kidneys. identify the instances GPS in hasplaced on which helped the the scheduled to flight.the kidney In kidney cases was can like be these, not quicklyment recovered and expedited the ship- recipient center. on a different flight to the Correspondence to Thomas D’Alessandro, NationalFire Kidney Registry, Island 42 Avenue, Babylon,fax: NY +1 11702, 800 USA. Tel: 401 +1 8919; 631Curr e-mail: 560 Opin [email protected] 7887; Organ Transplant DOI:10.1097/MOT.0000000000000669 Urology, David GeffenCalifornia, USA School of Medicine at UCLA, Los Angeles, With researchbetween cold ischemic demonstrating time (CIT)[3 and graft no failure correlation and Jeffrey L. Veale a Thomas D’Alessandro 2019 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ß KPD is a relativelyhigh-quality new living field donor and organs. the The innovations introduction itKeywords of has the spawned family should voucherkidney continue should transplantation, to continue paired improve this exchange, availability trend. transplant of Purpose of review To analyze the innovationsdonation that (KPD) have that increased has the led reliability, to convenience,Recent thousands and findings of outcomes living of donorOver kidney kidney the paired transplants past across 10cold the years, ischemia United KPD time, States. has research grownkidney has over and shown 200% the that on transplant thereovercome an outcome. is obstacles annual The no to basis. voucher correlation donation Though program between by concerns has travel solving had startedSummary time the existed to of issue over continue a of to shipped a expand pair how chronological to incompatibility. Innovations in kidney paired donation transplantation PINION URRENT O C longer were required toroundings leave to their participate preferred sur- in a kidney exchange. major surgery at aning apart unfamiliar from family hospital, and recover- living friends. The donor shipping of kidneysbarrier eliminated to this KPDmuch significant participation, larger pool andinnovation of resulted drastically donor/recipient inof increased pairs. a recipients This the finding likelihood a match, and donors no Perhaps the most significantin of KPD any advancement occurreddonor on kidney 30 was shipped July across theunaccompanied 2008, United States when on aBefore living this a sentinelelled commercial event, donors to airline typically their trav- KPD [2]. matched recipient’s city for ingly common approach to kidneyadvancements transplantation, and innovationsfurthered within that KPD growth10 have years by ago more (Fig. 1) than [1]. 200% from SHIPPING LIVING DONOR KIDNEYS By expanding the donor poolpatible and providing incom- pairs, andonor kidney opportunity transplant, topairs or receive an enabling akidney opportunity compatible paired living donation to (KPD) isvation receive a in remarkable a and inno- of better itself. As match, KPD becomes an increas- INTRODUCTION 1087-2418 Copyright

REVIEW

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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 failures 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.

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.

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 rooms/surgeons the much- CT images as their computers required special needed flexibility, and at the same time more con- viewing programs to be installed. Now images venience for donors who often have donation time of the kidney anatomy from the donor hospital constraints [13&&,14]. Vouchers take advanced dona- can be viewed by the recipient surgeon anywhere tion one-step further, as the intended recipients at any time with the click of the mouse through (voucher holders) are not yet in need of a kidney the NKR website. transplant and may never need a kidney transplant.

Additionally, voucher donors often function similar REFERENCES AND RECOMMENDED to nondirected donors and can trigger chains of READING Papers of particular interest, published within the annual period of review, have transplants, as they do not have a paired recipient been highlighted as: in the current chain (See Fig. 4). & of special interest Up to this point, donor/recipient pairs have only && of outstanding interest been considered incompatible by blood type or 1. Organ procurement and transplantation network. Available at: https://optn.- cross-match, however donor/recipient pairs can also transplant.hrsa.gov/. [Accessed 11 May 2019] 2. Butt FK, Gritsch HA, Schulam P, et al. Asynchronous, out-of-sequence, be incompatible by ‘time’ and the voucher concept transcontinental chain kidney transplantation: a novel concept. Am J Trans- helps resolve this ‘chronological incompatibility’ plant 2009; 9:2180–2185. && 3. Treat E, Chow EK, Peipert JD, et al. Shipping living donor kidneys and [13 ]. The natural next step in the voucher program && transplant recipient outcomes. Am J Transplant 2018; 18:632–641. is the ‘family-voucher.’ As some potential altruistic This study looked at shipped kidneys and transplant outcomes for KPD-facilitated living donor kidney transplants (LDKTs) and found no evidence that long CIT is a donors may be reluctant to donate a kidney in case a concern for reduced graft or patient survival. healthy family member (child/spouse) would need 4. National Kidney Registry (NKR) Public Website. Available at:. kidneyregistry.org. [Accessed 6 June 2019] it in the future. The family-voucher, launched by the 5. National Kidney Registry Administrative Database; transplants through 5/1/ NKR in 2019, enables an altruistic donor to voucher 19 [Accessed 6 June 2019]. 6. Johns Hopkins University School of Medicine, Department of Surgery; Kaplan- up to five healthy family members and one voucher Meier GS Rates for KPD (non-Chain End) Transplants Performed: 02/2008-06/ can be redeemed in the low likelihood one of the 2017 with follow-up through 12/31/2017. Available at: https://www.srtr.org/ SRTR. [Accessed June 2018] family members requires a kidney transplant in the 7. Flechner SM, Thomas AG, Ronin M, et al. The ﬁrst 9 years of kidney paired future [15]. && donation through the National Kidney Registry: Characteristics of donors and recipients compared with National Live Donor Transplant Registries. Am J Transplant 2018; 18:2730–2738. This research sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or CONCLUSION recipients compared with national registries. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible KPD is a relatively new field and the innovations it pairs and even chains initiated by deceased donors, to unlock more opportunities has spawned should continue to improve availabil- for those harder-to-match pairs. 8. Bingaman AW, Wright FH Jr, Kapturczak M, et al. Single-center kidney paired ity of high-quality living donor organs, outcomes donation: the methodist san antonio experience. Am J Transplant 2012; for recipients, convenience for donors, and better 12:2125–2132. 9. ‘National Kidney Registry Initiates Donor Blood Cryo-Preservation’ (Press process management for KPD and traditional living release). National Kidney Registry. 2 Dec 2014. Available at: https:// kidney donation alike. www.kidneyregistry.org/pages/p311/Cryo.php. [Accessed 6 June 2019] 10. Veale J, Hil G. The National Kidney Registry: 175 transplants in one year’. Clinical transplants. 2011; 255–278. 11. Kwak JY, Kwon OJ, Lee KS, et al. Exchange-donor program in renal trans- Acknowledgements plantation: a single-center experience. Transplant Proc 1999; 31:344–345. 12. Rees MA, Kopke JE, Pelletier RP, et al. A nonsimultaneous, extended, None. altruistic-donor chain. N Engl J Med 2009; 360:1096–1101. 13. Veale JL, Capron AM, Nassiri N, et al. Vouchers for future kidney transplants to && overcome ‘chronological incompatibility’ between living donors and recipi- Financial support and sponsorship ents. Transplantation 2017; 101:2115–2119. This study looked at shipped kidneys and transplant outcomes for KPD-facilitated LDKTs None. and found no evidence that long CIT is a concern for reduced graft or patient survival. 14. Flechner SM, Leeser D, Pelletier R, et al. The incorporation of an advanced donation program into kidney paired exchange: initial experience of the Conflicts of interest national kidney registry’. Am J Transplant 2015; 15:2712–2717. 15. National Kidney Registry. Advanced Donation. Program Empowering Living T.D. is the Chief Financial Officer of the NKR. J.V. is a Donation. Available at: https://kidneyregistry.org/pages/p500/Voucher_Bro- member of the NKR Medical Board. chure.php. [Accessed 17 June 2019]