255 CHAPTER 23 The National Kidney Registry: 175 Transplants in One Year Jeffrey Veale1 and Garet Hil2 1UCLA Department of Urology and 2National Kidney Registry Corresponding author: [email protected] Kidney paired donation and particularly the 180 175 increasing utilization of chains of transplants 160 initiated by a non-directed donor (NDD, 1-4) have 140 131 increased the number of living donor transplants 120 performed each year. Since facilitating its first 100 80 transplants in 2008, the National Kidney Registry 62 Transplants 60 (NKR) has organized more transplants than any 40 REGISTRY KIDNEY NATIONAL 21 other exchange program in the world. By the end 20 of 2011, NKR had facilitated 389 transplants, 0 including 175 in 2011 (Fig.1). The 2011 transplants 2008 2009 2010 2011 had an average wait time of 4.9 months from Figure 1. NKR Transplants Facilitated by Year. enrollment to transplant and included 49 patients 49 (28%) with cPRA scores >80% (Fig. 2). By working 50 with the majority of the top U.S. transplant centers 45 (by volume) and leveraging cutting edge computer 40 technology, the National Kidney Registry has 35 32 broken through many of the barriers that have 30 25 stalled other paired exchange efforts. Patients 20 THE NKR APPROACH 15 12 10 5 The NKR was started and is personally 1 0 managed by a dad who wanted to donate a kidney 2008 2009 2010 2011 to his daughter, but could not because he was Figure 2. Number of patients with cPRA >80% crossmatch incompatible. The frustrating search transplanted. for a compatible donor for his daughter, including logistics, technology, capital market systems and his attempted participation in every U.S. paired operations management. This experience proved exchange program existing in 2007, led him to critical in allowing for rapid evolution in these recognize that there had to be a better way to underdeveloped areas of paired exchange. The organize paired exchange transplants. team also relied on the active support and oversight Rapid innovation from an experienced Medical Board made up of transplant professionals. As a result, many bold NKR’s performance has benefited from the and technically difficult innovations have been start-up team’s deep industry experience in implemented, including: Clinical Transplants 2011, Terasaki Foundation Laboratory, Los Angeles, California 256 VEALE AND HIL • Implementation of Swap Expert, an artificial length of 20 deep, a staggering 10 to the 78th intelligence application for patient advice power of combinations are possible. Optimizing for • Creation of the Toolbox to determine preference ABO and HLA compatibility, age considerations, and avoid listing impact in real-time travel restrictions, additions of NDDs, additions of • Implementation of the donor pre-select function new pairs and other donor/recipient preferences to accept donors in advance of matches requires extremely sophisticated software for • Enhancement of real-time matching software finding and evaluating possible matches. allowing for 20+ deep match offers Over the past decade, different registries have • Use of Simultaneous Mutually Exclusive Loops developed a variety of computerized systems to and Chain matching (SMELAC) support multi-center loop and chain matching. • Introduction of a standardized financial model Most of the early systems were based on integer for centers to pay each other programming algorithms which were the best • Creation of a streamlined process to support tools to solve the complex mathematical problem CMS regulatory requirements presented by the traditional paired exchange • Utilization of a web portal for easy pair enrollment reciprocity requirement. With the advent of chains, and fast center startup these original integer programming solutions had to • Elimination of all personal health information be modified to accommodate the radically different avoiding HIPAA issues mathematical challenge presented by chains. The • Use of donor and recipient preferences to NKR system was initially created based solely control the match process on the chain matching model utilizing technology • Standardized identification and listing of all components employed by modern capital market relevant HLA antigens and antibodies exchange systems (e.g. New York Stock Exchange) • Inclusion of non-A1 donors to match O and B departing from integer programming algorithms patients with acceptable titers historically used for paired exchange. In 2011 • Real-time matching systems supporting the SMELAC algorithm was implemented, further immediate match identification and chain repair increasing the match capture rates by combining • Straight Through Processing for match offer loops and chains into a single search. Figure 3 tracking and process control illustrates how the SMELAC algorithm finds more • Utilization of existing infrastructure to ship matches. kidneys eliminating need for donor travel • Implementation of real-time geotracking Advanced matching strategies technology for shipped kidneys Clinical experience in paired exchange • Creation of children & high PRA program for demonstrates that the transplant center managing ending chains to patients without donors the donor/recipient pair has a significant impact Cutting edge computer technology on the probability of the pair finding a match in an exchange. Centers that have implemented the As the length of the matched clusters that advanced matching strategies (Table 1) supported make up the segments of each transplant chain by the Toolbox and Swap Expert decision support is extended, the number of transplants that can systems are able to transplant significantly more be facilitated increases dramatically. For example, patients through paired exchange, indicating a pool of 100 incompatible donor/recipient that there is a material center effect at work in pairs running a 3-deep cluster will generate paired exchange. We are seeing paired exchange approximately 10 billion combinations. If the length centers of excellence emerge as patients become of the cluster increases by just one, to 4-deep, the more aware of, and seek out those centers that number of possible combinations increases to 100 demonstrate superior performance in paired trillion. Utilizing software that can find a cluster exchange. 257 SMELAC Finds More Matches SMELAC = Simultaneous mutually exclusive loops and chain Loop Only Chain Only SMELAC Pool Matching Matching Matching Pair A Pair A Pair A Pair A Pair B Pair D Pair B Pair E Pair C -- OR -- Pair D Pair C Pair D Pair B -- OR -- -- AND -- Pair E Pair D Pair A Pair B Pair E Pair D Pair D Matches 5 2 3 5 REGISTRY KIDNEY NATIONAL % of Pool - 40% 60% 100% Matched Figure 3. SMELAC finds more matches. the live pool information. The Toolbox Table 1. Advanced Matching Strategies, transplanting hard-to-match recipients. automates the metrics for calculating • Utilize non A1 donors for O and B recipients with acceptable titers the pair match power based on all of the • Include compatible pairs in swaps (e.g. O donors with non A donors and recipients active in the pool recipients) at any given time. To determine the pair • Utilize NKR ToolBox and Swap Expert decision support systems • Relax preference restrictions (e.g. accept shipped kidney, etc.) match power, the recipient is evaluated based on pair match power sensitivities to determine how many donors in the • Raise MFI thresholds - combine with desensitization protocols for pool match them, and the paired donor highly sensitized recipients • Utilize multiple paired donors – O donors are 10X more powerful in is evaluated to determine how many a swap recipients in the pool they match. The • Start chains and take advantage of the NKR CHIP program to get recipient score and donor score are patients without donors transplanted • Increase pool size by enrolling more pairs at your center and then multiplied against each other to encouraging other centers to join. determine the pair’s match power. This • Reach out using center hosted seminars on paired exchange, call score defines how easy or hard it will all patients on wait list and educate pairs upon initial intake. be to find a match in the NKR program Online decision support tools and is the basis of determining which The Toolbox advanced matching strategies should be employed to get the patient transplanted. The Toolbox module (Fig. 4) was implemented in The Toolbox also facilitates the automated 2011 to provide information that allows participating upload of high resolution antibody information centers to leverage advanced matching strategies (MFI values) supporting sensitivity analysis for and to provide real-time feedback to transplant unacceptable HLA antigen listing strategies. The centers regarding a pair’s match power and the automated upload also eliminates the data entry impact different preference settings and avoid errors which are prevalent when entering avoids listings can have on the pair match power using 258 VEALE AND HIL for highly sensitized patients and therefore reduces cross match failures. Donor pre-select The donor pre-select module (Fig. 5) was also introduced in 2011 and allows for the review, acceptance or rejection of all donors that match a given recipient in the NKR system. This feature has dramatically reduced the number of failed match offers and gives the transplant centers specific information on donors in advance of a match offer so that informed medical decisions can be made regarding the suitability of donors for any given recipient. Swap expert The Swap Expert (Fig. 6) is an artificial intelligence application that helps transplant centers and patients decide on preference settings and matching strategies Figure 4. The Toolbox. that maximize compatibility while automated output, NKR staff reviews this output minimizing wait time. The Swap Expert leverages with Member Centers to train medical staff on the the matching knowledge accumulated by the NKR nuances of paired exchange matching strategies. staff and delivers it in a usable form to patients and transplant centers. In addition to the Swap Expert’s Donor Pre-Select - Summary Donor Pre-Select - Detail Figure 5. Donor pre-select software. A. summary screen, B. donor pre-select - detail.