Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Early vs Single Match in the Transition to Residency: Analysis Using NRMP Data From 2014 to 2021.

Background: An Early Result Acceptance Program (ERAP) has been proposed for obstetrics and gynecology (OB/GYN) to address challenges in the transition to residency. However, there are no available data-driven analyses on the effects of ERAP on the residency transition. Objective: We used National Resident Matching Program (NRMP) data to simulate the outcomes of ERAP and compare those to what occurred in the Match historically. Methods: We simulated ERAP outcomes in OB/GYN, using the de-identified applicant and program rank order lists from 2014 to 2021, and compared them to the actual NRMP Match outcomes. We report outcomes and sensitivity analyses and consider likely behavioral adaptations. Results: Fourteen percent of applicants receive a less preferred match under ERAP, while only 8% of applicants receive a more preferred match. Less preferred matches disproportionately affect DOs and international medical graduates (IMGs) compared to US MD seniors. Forty-one percent of programs fill with more preferred sets of applicants, while 24% fill with less preferred sets of applicants. Twelve percent of applicants and 52% of programs are in mutually dissatisfied applicant-program pairs (a pair in which both prefer each other to the match each received). Seventy percent of applicants who receive less preferred matches are part of a mutually dissatisfied pair. In 75% of programs with more preferred outcomes, at least one assigned applicant is part of a mutually dissatisfied pair. Conclusions: In this simulation, ERAP fills most OB/GYN positions, but many applicants and programs receive less preferred matches, and disparities increase for DOs and IMGs. ERAP creates mutually dissatisfied applicant-program pairs and problems for mixed-specialty couples, which provides incentives for gamesmanship.

Living Kidney Donor Transplantation and Global Kidney Exchange.

Global kidney exchange offers an opportunity to expand living donor kidney transplants internationally to patients with immunologic barriers. The concept has been proven to be successful in a limited number of transplants. However, a number of misconceptions have created obstacles to its development. We suggest that a systematic application of this innovative tool would offer opportunities to treat thousands of patients worldwide who are presently denied a transplant and often even access to dialysis.

Global kidney chains.

Kidney failure is a worldwide scourge, made more lethal by the shortage of transplants. We propose a way to organize kidney exchange chains internationally between middle-income countries with financial barriers to transplantation and high-income countries with many hard to match patients and patient-donor pairs facing lengthy dialysis. The proposal involves chains of exchange that begin in the middle-income country and end in the high-income country. We also propose a way of financing such chains using savings to US health care payers.

Non-simultaneous kidney exchange cycles in resource-restricted countries without non-directed donation - a prospective single-center cohort study.

Recent reports suggest that bridge-donor reneging is rare (1.5%) in non-simultaneous kidney exchange chains. However, in developing countries, the non-directed donors who would be needed to initiate chains are unavailable, and furthermore, limited surgical space and resources restrain the feasibility of simultaneous kidney exchange cycles. Therefore, the aim of this study was to evaluate the bridge-donor reneging rate during non-simultaneous kidney exchange cycles (NSKEC) in a prospective single-center cohort study (n = 67). We describe the protocol used to prepare co-registered donor-recipient pairs for non-simultaneous surgeries, in an effort to minimize the reneging rate. In addition, in order to protect any recipients who might be left vulnerable by this arrangement, we proposed the use of standard criteria deceased-donor kidneys to rectify the injustice in the event of any bridge-donor reneging. We report 17 successful NSKEC resulting in 67 living-donor kidney transplants (LDKT) using 23 bridge-donors without donor renege and no intervening pairs became unavailable. We propose that NSKEC could increase LDKT, especially for difficult-to-match sensitized pairs (25 of our 67 pairs) in countries with limited transplantation resources. Our study confirms that NSKEC can be safely performed with careful patient-donor selection and non-anonymous kidney exchanges.

Promoting Ethical Payment in Human Infection Challenge Studies.

To prepare for potential human infection challenge studies (HICS) involving SARS-CoV-2, we convened a multidisciplinary working group to address ethical questions regarding whether and how much SARS-CoV-2 HICS participants should be paid. Because the goals of paying HICS participants, as well as the relevant ethical concerns, are the same as those arising for other types of clinical research, the same basic framework for ethical payment can apply. This framework divides payment into reimbursement, compensation, and incentives, focusing on fairness and promoting adequate recruitment and retention as counterweights to concerns about undue inducement. Within the basic framework, several factors are especially salient for HICS, and for SARS-CoV-2 HICS in particular, including the nature of participant confinement, anticipated discomfort, risks and uncertainty, participant motivations, and trust. These factors are reflected in a payment worksheet created to help sponsors, researchers, and ethics reviewers systematically develop and assess ethically justifiable payment amounts.

Popular repugnance contrasts with legal bans on controversial markets.

We study popular attitudes in Germany, Spain, the Philippines, and the United States toward three controversial markets-prostitution, surrogacy, and global kidney exchange (GKE). Of those markets, only prostitution is banned in the United States and the Philippines, and only prostitution is allowed in Germany and Spain. Unlike prostitution, majorities support legalization of surrogacy and GKE in all four countries. So, there is not a simple relation between public support for markets, or bans, and their legal and regulatory status. Because both markets and bans on markets require social support to work well, this sheds light on the prospects for effective regulation of controversial markets.

The 6-year clinical outcomes for patients registered in a multiregional United States Kidney Paired Donation program - a retrospective study.

We examined what happened during a 6-year period to 1121 end-stage renal disease patients who registered with their willing/incompatible living donors for kidney exchanges with the Alliance for Paired Donation (APD). Of all patients, 65% were transplanted: 37% in kidney paired donation (APD-KPD, APD-other-KPD); 10% with compatible live donors (APD-LD); and 18% with deceased donors (APD-DD). The remaining patients were withdrawn (sick/died/others; 15%), or were still waiting (20%). For those patients with a cPRA 0-94%, 72% received a transplant. In contrast, only 49% of very highly sensitized (VHS; cPRA 95-100%) were transplanted. Of the VHS patients, 50% were transplanted by KPD/APD-LD while 50% benefited through prioritization of deceased donors in the modified kidney allocation system (KAS introduced in 2014). All APD transplanted groups had similar death-censored 4-year graft survivals as their relevant Organ Procurement and Transplantation Network (OPTN) groups. It is noteworthy that VHS graft and patient survival results were comparable to less sensitized and nonsensitized patients. All patients should be encouraged to search for compatible donors through different options. Expanding the donor pool through KPD and the new KAS of the OPTN increases the likelihood of transplantation for VHS patients.

Complete Chain of the First Global Kidney Exchange Transplant and 3-yr Follow-up.

BACKGROUND: Global Kidney Exchange (GKE) offers an opportunity to expand living renal transplantation internationally to patients without financial means. These international pairs are entered into a US kidney exchange program that provides long-term financial support in an effort to identify opportunities for suitable exchanges for both these international pairs and US citizens. OBJECTIVE: While the promise of GKE is significant, it has been met with ethical criticism since its inception in 2015. This paper aims to demonstrate the selection process and provide >3 yr of follow-up on the first GKE donor and recipient from the Philippines. DESIGN, SETTING, AND PARTICIPANTS: The first GKE transplant occurred with a young Filipino husband and wife who were immunologically compatible, but lacked the financial means to continue hemodialysis or undergo a kidney transplant in their home country. The pair was enrolled in the Alliance for Paired Donation matching system, several alternative kidney exchanges were identified, and the pair subsequently underwent renal transplantation and donation in the USA financed by philanthropy. The resulting nonsimultaneous extended altruistic chain provided transplantation for the Filipino husband and 11 US patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Filipino donor and recipient were followed by transplant professionals in both the Philippines and the USA. Follow-up data were maintained as required by the Organ Procurement and Transplantation Network in the USA. RESULTS AND LIMITATIONS: The Filipino donor has normal blood pressure and renal function, and the Filipino recipient is doing well 3.5 yr after their donation and transplantation. CONCLUSIONS: While criticisms of GKE highlight concerns for possible exploitation of financially disadvantaged groups, these results demonstrate that these concerns did not come to fruition, and the outcome experienced by the GKE donor and recipient (and other US participants) was successful. PATIENT SUMMARY: The first Filipino Global Kidney Exchange (GKE) donor-recipient pair continues to be followed by both US and Filipino transplant centers. Both are in good health, support the GKE program, and advocate for its expansion.

Marketplaces, Markets, and Market Design.

Marketplaces are often small parts of large markets, and both markets and marketplaces come in many varieties. Market design seeks to understand what marketplaces must accomplish to enable different kinds of markets. Marketplaces can have varying degrees of success, and there can be marketplace failures. I'll discuss labor markets like the market for new economists, and also markets for new lawyers and doctors that have suffered from the unraveling of appointment dates to well before employment begins. Markets work best if they enjoy social support, but some markets are repugnant in the sense that some people think they should be banned, even though others want to participate in them. Laws banning such markets often contribute to the design of illegal black markets, and this raises new issues for market designers. I'll briefly discuss markets and black markets for narcotics, marijuana, sex, and surrogacy, and the design of markets for kidney transplants, in the face of widespread laws against (and broader repugnance for) compensating organ donors. I conclude with open questions and engineering challenges.

Effect of match-run frequencies on the number of transplants and waiting times in kidney exchange.

Numerous kidney exchange (kidney paired donation [KPD]) registries in the United States have gradually shifted to high-frequency match-runs, raising the question of whether this harms the number of transplants. We conducted simulations using clinical data from 2 KPD registries-the Alliance for Paired Donation, which runs multihospital exchanges, and Methodist San Antonio, which runs single-center exchanges-to study how the frequency of match-runs impacts the number of transplants and the average waiting times. We simulate the options facing each of the 2 registries by repeated resampling from their historical pools of patient-donor pairs and nondirected donors, with arrival and departure rates corresponding to the historical data. We find that longer intervals between match-runs do not increase the total number of transplants, and that prioritizing highly sensitized patients is more effective than waiting longer between match-runs for transplanting highly sensitized patients. While we do not find that frequent match-runs result in fewer transplanted pairs, we do find that increasing arrival rates of new pairs improves both the fraction of transplanted pairs and waiting times.