The idea for a kidney exchange program was expressed by Dr. Felix Rapaport in 1986; since then, it has been increasing all over the world. This article discusses the indications of kidney paired donation and how it proved to be the best option for living donation, the innovations done for its expansion over the years, and how to adopt it in countries deprived of this service, highlighting the measures it takes for its implementation and the drawbacks of its nonexistence.

Key words : Living organ donation, Organ shortage, Organ transplant exchange program

Introduction
Organ shortage is a big problem the world is facing, with the ever-widening gap between the increasing numbers of patients with end-stage kidney disease and the availability of organs for donation. Every effort should be taken to expand the donor pool.

When kidney paired donation (KPD) first started, it was meant to provide organs for unmatched donors with regard to the ABO system and HLA antigens, as well as for patients sensitized from previous transplants, blood transfusions, or pregnancy.¹ These patients, especially those highly sensitized, will most likely remain on the wait list for a long time, with neither the opportunity to acquire a living donor kidney, which lasts longer than a deceased donor kidney, nor the benefit of the virtues of preemptive transplant compared with long-term dialysis.²

With the expansion of the KPD programs to involve more countries over the world, thus increasing the pool of donor-recipient pairs for exchange, and with the use of highly sophisticated algorithms to select transplant exchanges,³ it has become possible to accommodate difficult-to-match patients and also to optimize the match.⁴ These aspects are important because antigen match matters (especially with 6 antigen matches) and donor age also matters (especially for those older than 65 years).

Therefore, KPD programs not only provide compatible donors for unmatched or sensitized patients, but also allow for a better match in already-compatible couples, as well as a better transplant quality. These aspects are validated by the superior patient and graft outcomes that result from KPD programs.

Innovations
With the realization of the importance of KPD programs, measures have been undertaken for its expansion. The most significant of any advancement in KPD occurred in 2008, when a living donor kidney was shipped across the United States, unaccompanied, on a commercial airline; thus, donors were spared the trouble of travelling to another city to undergo a transplant far away from family and friends. This benefit of accessibility increased the willingness of directed living donors and their recipients to participate in KPD programs,⁵ especially with the evidence that cold ischemia time up to 16 hours does not undermine the outcome.⁶ Shipping organs is now an established standard and has resulted in a much larger donor pool.

Another achievement of the development of the KPD model is the voucher, which resolves the problem of timely expedience for donor-recipient incompatibility by features such as advanced donation and organ banking. With advanced donation, procurement may be scheduled for a time that is most convenient for the donor, even if the donor’s eventual paired recipient has not yet been matched for suitability or scheduled for surgery.⁷ With banking, the donor may undergo surgery even before the eventual recipient is in need for transplantation, and this aspect is especially valuable for a scenario in which a donor is unlikely to be able to donate at a future time.⁸ In these situations, the donor donates to the paired exchange program, with a commitment to the specified recipient to have a priority access for a living donor transplant in a paired exchange program once needed.

Another important voucher is the donor shield, whereby donors are encouraged by the offer of benefits, such as financial reimbursement for lost wages, expenses for travel and lodging, kidney prioritization in the unlikely event that the donor ever needs a kidney, donation, insurance, legal support, and other incentives.⁵

Marked innovations have also been achieved in the laboratory as well as mathematical and logistical optimizations, all of which have increased the convenience and speed of the paired exchange process.

Adoption of a kidney paired donation program and drawbacks of its nonexistence

To start a KPD program,⁹ it is mandatory to have a national organization, with a single database of all recipients and donors, and this organization should also encourage donors by various methods of reimbursement.

It is crucial to identify hospitals with transplant centers to participate in the program. There must be a high level of coordination between these hospitals and the national organization. An allocation system must be established that is both medically sound and ethically fair. Software platforms can easily be obtained. Another crucial consideration is standardization of laboratory protocols and imaging systems on a national basis. Donor follow-up clinics must be established, staffed, and funded.

A KPD program can be started with a simple plan and on a small scale, starting from where other previous attempts ended.

Without a KPD program, the options for patients who remain without compatible donors will be (1) to remain on dialysis for the rest of their lives, jeopardizing their quality of life and years of survival, or (2) enroll on the wait list for a deceased donor program, if any, which means long years of wait time and loss of the advantages of preemptive transplant and living donation.^2,10 Desensitization programs for sensitized patients can also be established, which requires the use of potent drugs, with side effects and high cost, and still a high incidence of antibody-mediated rejection and risk of graft loss.¹¹

In a scenario where there is no opportunity for deceased transplant, no compatible living donor, and no KPD program, the final transplant option for some patients could be commercial transplant, which is not ethical, completely discouraged, and should be prohibited.

Conclusions
Kidney paired donation is a remarkable innovation in and of itself. A KPD program has the following advantages: greater number of kidneys available for transplant; improved opportunity for the most incompatible candidates to find matches and receive transplants; optimization of the matches for already-matched couples; avoidance of the health risks and financial costs of desensitization strategies designed to remove anti-donor antibodies; reduction of wait times on national transplant lists; provision of living donor grafts, which are usually superior to deceased donor grafts; and cessation of commercial transplants.

A robust KPD program is the best option for living donation and should be considered for all potential living donors.

References:

1. Ferrari P, Weimar W, Johnson RJ, Lim WH, Tinckam KJ. Kidney paired donation: principles, protocols and programs. Nephrol Dial Transplant. 2015;30(8):1276-1285. doi:10.1093/ndt/gfu309
   CrossRef - PubMed
   
2. Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation. 2002;74(10):1377-1381. doi:10.1097/00007890-200211270-00005
   CrossRef - PubMed
   
3. Bray M, Wang W, Rees M, et al. A visualization software platform for managing a kidney paired-donation program (Abstract). Am J Transplant. 2016;16(suppl 3):D182. https://atcmeetingabstracts.com/abstract/a-visualization-software-platform-for-managing-a-kidney-paired-donation-program/
   CrossRef - PubMed
   
4. Ferrari P, Cantwell L, Ta J, Woodroffe C, D’Orsogna L, Holdsworth R. Providing better-matched donors for HLA mismatched compatible pairs through kidney paired donation. Transplantation. 2017;101(3):642-648. doi:10.1097/TP.0000000000001196
   CrossRef - PubMed
   
5. Hendren E, Gill J, Landsberg D, Dong J, Rose C, Gill JS. Willingness of directed living donors and their recipients to participate in kidney paired donation programs. Transplantation. 2015;99(9):1894-1899. doi:10.1097/TP.0000000000000533
   CrossRef - PubMed
   
6. Flechner SM, Leeser D, Pelletier R, et al. The incorporation of an advanced donation program into kidney paired exchange: initial experience of the national kidney registry. Am J Transplant. 2015;15(10):2712-2717. doi:10.1111/ajt.13339
   CrossRef - PubMed
   
7. Nassiri N KL, Bolagani A, et al. The “oldest and coldest” shipped living donor kidneys transplanted through kidney paired donation. Am J Transplant.20(1):137-144. doi:10.1111/ajt.15527
   CrossRef - PubMed
   
8. Martin DE, Danovitch GM. Banking on living kidney donors: a new way to facilitate donation without compromising on ethical values. J Med Philos. 2017;42(5):537-558. doi:10.1093/jmp/jhx015
   CrossRef - PubMed
   
9. Elrggal ME TM, Gawad MA, Sheasha HA. Kidney paired donation program, a national solution against commercial transplantation? J Egypt Soc Nephrol Transplant. 2018;18(1):6-10. doi:10.4103/jesnt.jesnt_1_18
   CrossRef - PubMed
   
10. Matas AJ, Smith JM, Skeans MA, et al. OPTN/SRTR 2012 annual data report: kidney. Am J Transplant. 2014;14 Suppl 1:11-44. doi:10.1111/ajt.12579
    CrossRef - PubMed
    
11. Tambur AR, Campbell P, Claas FH, et al. Sensitization in Transplantation: Assessment of Risk (STAR) 2017 working group meeting report. Am J Transplant. 2018;18(7):1604-1614. doi:10.1111/ajt.14752
    CrossRef - PubMed