Kidney Paired Donation Pool Research Articles

Kidney Paired Donation Chains Initiated by Deceased Donors

IntroductionRather than generating 1 transplant by directly donating to a candidate on the waitlist, deceased donors (DDs) could achieve additional transplants by donating to a candidate in a kidney paired donation (KPD) pool, thereby, initiating a chain that ends with a living donor (LD) donating to a candidate on the waitlist. We model outcomes arising from various strategies that allow DDs to initiate KPD chains.MethodsWe base simulations on actual 2016 to 2017 US DD and waitlist data and use simulated KPD pools to model DD-initiated KPD chains. We also consider methods to assess and overcome the primary criticism of this approach, namely the potential to disadvantage blood type O-waitlisted candidates.ResultsCompared with shorter DD-initiated KPD chains, longer chains increase the number of KPD transplants by up to 5% and reduce the number of DDs allocated to the KPD pool by 25%. These strategies increase the overall number of blood type O transplants and make LDs available to candidates on the waitlist. Restricting allocation of blood type O DDs to require ending KPD chains with LD blood type O donations to the waitlist markedly reduces the number of KPD transplants achieved.ConclusionAllocating fewer than 3% of DD to initiate KPD chains could increase the number of kidney transplants by up to 290 annually. Such use of DDs allows additional transplantation of highly sensitized and blood type O KPD candidates. Collectively, patients of each blood type, including blood type O, would benefit from the proposed strategies.

Deceased donors as nondirected donors in kidney paired donation.

As proof of concept, we simulate a revised kidney allocation system that includes deceased donor (DD) kidneys as chain-initiating kidneys (DD-CIK) in a kidney paired donation pool (KPDP), and estimate potential increases in number of transplants. We consider chains of length 2 in which the DD-CIK gives to a candidate in the KPDP, and that candidate's incompatible donor donates to theDD waitlist. In simulations, we vary initial pool size, arrival rates of candidate/donor pairs and (living) nondirected donors (NDDs), and delay time from entry to the KPDP until a candidate is eligible to receive a DD-CIK. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Kidney Donation, and the actual DDs from the Scientific Registry of Transplant Recipients (SRTR) data, simulations extend over 2years. With an initial pool of 400, respective candidate and NDD arrival rates of 2 per day and 3 per month, and delay times for access to DD-CIK of 6months or less, including DD-CIKs increases the number of transplants by at least 447 over 2years, and greatly reduces waiting times of KPDP candidates. Potential effects on waitlist candidates are discussed as are policy and ethical issues.

KPDGUI: An interactive application for optimization and management of a virtual kidney paired donation program

Background and objectivesThe aim in kidney paired donation (KPD) is typically to maximize the number of transplants achieved through the exchange of donors in a pool comprising incompatible donor-candidate pairs and non-directed (or altruistic) donors. With many possible options in a KPD pool at any given time, the most appropriate set of exchanges cannot be determined by simple inspection. In practice, computer algorithms are used to determine the optimal set of exchanges to pursue. Here, we present our software application, KPDGUI (Kidney Paired Donation Graphical User Interface), for management and optimization of KPD programs. MethodsWhile proprietary software platforms for managing KPD programs exist to provide solutions to the standard KPD problem, our application implements newly investigated optimization criteria that account for uncertainty regarding the viability of selected transplants and arrange for fallback options in cases where potential exchanges cannot proceed, with intuitive resources for visualizing alternative optimization solutions. ResultsWe illustrate the advantage of accounting for uncertainty and arranging for fallback options in KPD using our application through a case study involving real data from a paired donation program, comparing solutions produced under different optimization criteria and algorithmic priorities. ConclusionsKPDGUI is a flexible and powerful tool for offering decision support to clinicians and researchers on possible KPD transplant options to pursue under different user-specified optimization schemes.

Combinatorial Hodge theory for equitable kidney paired donation

Kidney Paired Donation (KPD) is a system whereby incompatible patient-donor pairs (PD pairs) are entered into a pool to find compatible cyclic kidney exchanges where each pair gives and receives a kidney. The donation allocation decision problem for a KPD pool has traditionally been viewed within an economic theory and integer-programming framework. While previous allocation schema work well to donate the maximum number of kidneys at a specific time, certain subgroups of patients are rarely matched in such an exchange. Consequently, these methods lead to systematic inequity in the exchange, where many patients are rejected a kidney repeatedly. Our goal is to investigate inequity within the distribution of kidney allocation among patients, and to present an algorithm which minimizes allocation disparities. The method presented is inspired by cohomology and describes the cyclic structure in a kidney exchange efficiently; this structure is then used to search for an equitable kidney allocation. Another key result of our approach is a score function defined on PD pairs which measures cycle disparity within a KPD pool; i.e., this function measures the relative chance for each PD pair to take part in the kidney exchange if cycles are chosen uniformly. Specifically, we show that PD pairs with underdemanded donors or highly sensitized patients have lower scores than typical PD pairs. Furthermore, our results demonstrate that PD pair score and the chance to obtain a kidney are positively correlated when allocation is done by utility-optimal integer programming methods. In contrast, the chance to obtain a kidney through our method is independent of score, and thus unbiased in this regard.

Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors.

With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy.

MP79-12 HOW LONG IS TOO LONG? AN ANALYSIS OF THE IMPACT OF BRIDGE DONOR WAITING TIME ON PAIRED DONATION TRANSPLANTS

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2015MP79-12 HOW LONG IS TOO LONG? AN ANALYSIS OF THE IMPACT OF BRIDGE DONOR WAITING TIME ON PAIRED DONATION TRANSPLANTS David Fumo, Timothy Suttle, Ryan Flynn, Laurie Reece, Stanislaw Stepkowski, Michael Rees, and Jonathan Kopke David FumoDavid Fumo More articles by this author , Timothy SuttleTimothy Suttle More articles by this author , Ryan FlynnRyan Flynn More articles by this author , Laurie ReeceLaurie Reece More articles by this author , Stanislaw StepkowskiStanislaw Stepkowski More articles by this author , Michael ReesMichael Rees More articles by this author , and Jonathan KopkeJonathan Kopke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2869AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Non-simultaneous Extended Altruistic Donor (NEAD) chains and bridge donors (BD) are increasingly utilized in the field of Kidney Paired Donation (KPD), but remain controversial due to the possibility that such donors could renege on their promise to donate a kidney. The donor at the end of a NEAD chain is referred to as a BD, who is re-entered into the pool and trusted to donate after their incompatible recipient has received a transplant. This study evaluates how long bridge donors should wait. METHODS Data from a single United States KPD matching program was analyzed. To understand the impact of a BD subsequently failing to donate, a theoretical model was created in which a wait time limit (WTL) was placed on BDs. If the WTL was reached, the bridge donor was directed to the deceased donor waitlist and the chain was ended. If the WTL was not reached before a donor reneged, the chain ended with no additional transplant to the deceased donor waitlist. RESULTS A total of 90 BDs were used in 26 NEAD chains to complete 151 transplants. Nine BDs (10%) are currently suspended or withdrawn from the KPD pool. Though some of these donors may eventually donate, for the purpose of this study they were considered to have reneged. Of these 9 BD who appear to have reneged most were subsequently denied as donors for medical reasons; only 2 of 90 (2.2%) simply chose not to donate. No BD in a planned NEAD chain has failed to donate, so only BDs without initially identified potential recipients were included in the model (n=61). The maximum number of transplants was achieved with a WTL of 365 days (Figure 1), which would have resulted in 152 transplants/6 reneged BDs. By comparison, an unlimited WTL resulted in 148 transplants/9 reneges, while not allowing BDs to wait (WTL=0) would have achieved 89 transplants/0 reneges. The most significant gains in the number of transplants were seen with a WTL between 120 and 210 days (97 to 144 transplants). Four BDs reneged at 210 days, with an additional 2 reneging between 210 and 365 days. CONCLUSIONS This data suggests that a reasonable BD WTL should be at least 7 months, but not more than 1 year. To date, most BD reneging is actually medical disqualification, rather than a choice by the donor not to donate. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1015 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Fumo More articles by this author Timothy Suttle More articles by this author Ryan Flynn More articles by this author Laurie Reece More articles by this author Stanislaw Stepkowski More articles by this author Michael Rees More articles by this author Jonathan Kopke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Rescue Kidney Paired Donation as Emergency Salvage for Failed Desensitization

Rescue Kidney Paired Donation as Emergency Salvage for Failed Desensitization

Using donor exchange paradigms with desensitization to enhance transplant rates among highly sensitized patients

Many sensitized patients have willing live donors but are unable to use them because of a human leukocyte antigen (HLA) incompatibility. The options for these patients include: remaining on the deceased-donor list, entering a kidney-paired donation scheme, or undergoing desensitization with high-dose IVIg or plasmapheresis and low-dose IVIg. Mathematical simulations verified by actual data from several national kidney-paired donation (KPD) programs has shed light on which donor/recipient phenotypes are likely to benefit from each transplant modality. Pairs that are easy to match are likely to receive compatible kidneys in a KPD. Those who are hard to match may be better served by desensitization. The phenotype which is both hard to match and hard to desensitize due to board and strong HLA reactivity are most likely to be transplanted by a hybrid modality utilizing desensitization after identifying a more immunologically favorable donor in a KPD. Recent outcomes from desensitization in which starting donor-specific antibody strength is low have been very good. For broadly sensitized patients with a high-strength cross-match, searching for a better donor in a KPD pool can facilitate a safer, less expensive, and more successful desensitization treatment course.

Renal Transplantation Across HLA and ABO Antibody Barriers: Integrating Paired Donation into Desensitization Protocols

The field of desensitization and incompatible transplantation has made great gains over the past decade. There are now several options and effective therapies for many patients who face antibody barriers. Kidney paired donation (KPD) and desensitization have traditionally been considered competing strategies and patients have been offered one or the other without regard for the probability of a successful outcome. It is now possible to predict which donor/recipient phenotypes will benefit from each of these modalities. KPD should be favored among patients with immunologic phenotypes that are likely to match without prolonged waiting times. However, as many as 50% of patients with incompatible donors will fail to find a match in a KPD pool and many of these patients could be desensitized to their donor. Positive crossmatch and ABO incompatible transplantation has been accomplished in selective cases without the need for heavy immunosuppression or B-cell ablative therapy. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of strong donor reactivity can often be successfully transplanted through a combination of desensitization and KPD. Using these various modalities it is estimated that most patients with incompatible live donors can undergo successful renal transplantation.

Working Together Toward a National Kidney Paired Donation Program

To the Editor: Many researchers have addressed compatible pair participation in kidney paired donation (KPD) programs. The concept was first introduced by Woodle and Ross (1Woodle ES Ross LF Paired exchanges should be part of the solution to ABO incompatibility in living donor kidney transplantation.Transplantation. 1998; 66: 406-407Crossref PubMed Scopus (19) Google Scholar) and first implemented clinically by Montgomery et al. (2Montgomery RA Zachary AA Ratner LE et al.Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation.JAMA. 2005; 294: 1655-1663Crossref PubMed Scopus (164) Google Scholar). Comprehensive inclusion of compatible pairs in clinical KPD programs would nonetheless be a new paradigm, as evidenced by ongoing contention in the transplant community about whether to pursue compatible paired donation. In their 2006 discourses, Veatch (3Veatch RM Why organ exchanges serve the interests of Odonors.Am J Transplant. 2006; 6: 856Crossref Scopus (3) Google Scholar) and Spital (4Spital A Veatch’s proposal may not work.Am J Transplant. 2006; 6 (author reply 856): 855Crossref Scopus (5) Google Scholar) each referred to the unknown probability that a compatible pair could benefit from KPD. The goal of our recent manuscript (5Gentry SE Segev DL Simmerling M Montgomery RA Expanding kidney paired donation through participation by compatible pairs.Am J Transplant. 2007; 7: 2361-2370Crossref PubMed Scopus (122) Google Scholar) was to estimate this controversial probability and how it might vary depending on the size and makeup of KPD programs and on the precise definition of benefit. These questions had never been answered. Roth et al. previously suggested that compatible pairs would increase matching opportunities in KPD (6Roth AE Sönmez T ünver MU A kidney exchange clearinghouse in New England.Am Econ Rev. 2005; 95: 376-380Crossref PubMed Scopus (164) Google Scholar). However, because of methodologic limitations, Roth et al. could not address the critical issue later identified by Veatch and Spital. The maximum cardinality-matching algorithm used by Roth et al. assumes that all matches are equally valuable, and as such cannot capture distinctions such as matching to a beneficial donor versus matching to a medically inferior one. The top-trading-cycles algorithm used by Roth et al. requires logistically impossible 26-way matches. In their letter to which we respond, Roth et al. (7Roth AE, Söonmez T, ünver MU. Kidney paired donation with com-patible pairs. Am J Transplant (in press).Google Scholar) describe one difference between our analysis and theirs (that their model considers only unrelated donors) but do not mention the more fundamental contrast and its implications. Rather than maximum cardinality matching, which seeks to maximize the number of transplants, we use maximum edge-weight matching that considers the quality of the matches. Although both algorithms were suggested by Edmonds, only maximum edge-weight matching can respect factors such as varying levels of medical benefit to a recipient who enters KPD with his compatible donor. Furthermore, only maximum edge-weight matching can prioritize local and regional matches. Minimizing travel was a central feature of the UNOS proposal for KPD, and the UNOS consensus statement acknowledged that such prioritization would require edge weighting. Moreover, we have recently shown that it is possible to design maximum edge-weight models so that they will also include the maximum number of transplants, if that is desired. The purpose of our study was to demonstrate the high probability that a compatible pair entering a KPD pool would derive a benefit in terms of younger donor age and better matching, because that fact might encourage a widening of compatible pair participation. This is very different from previous simulation work by Roth et al. concerning compatible pairs in KPD pools, but we did not intend to overlook their contributions. We applaud the interest of economists in the field of transplantation. Our interest has been in developing mathematical models that closely reflect actual medical practice. A national KPD program would yield the greatest benefit to the largest number of patients awaiting transplantation. It is our hope that the transplant community will unite behind the cause of making KPD available to all patients by supporting a national program administered through UNOS.

Clinical Results From Transplanting Incompatible Live Kidney Donor/Recipient Pairs Using Kidney Paired Donation

First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. Kidney paired donation and live donor renal transplantation. Patient survival, graft survival, serum creatinine levels, rejection episodes. A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.