175 Transplants in One Year Jeffrey Veale1 and Garet Hil2 1UCLA Department of Urology and 2National Kidney Registry Corresponding Author: [email protected]

175 Transplants in One Year Jeffrey Veale1 and Garet Hil2 1UCLA Department of Urology and 2National Kidney Registry Corresponding Author: Gh@Kidneyregistry.Org

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 NATIONAL KIDNEY REGISTRY 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 NATIONAL KIDNEY REGISTRY

% 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. 259

Standardized listing of all

NKR Swap Expert relevant HLA antigens and Patient Advisory for BROD antibodies Enter Missing Information: (There is no missing information.) 1. Manage Antibody Avoids: You have a significant number (35) of antibody avoids recorded in the system. These avoids combined with blood type incompatibility are When the NKR program was blocking matches with 98.4% of the 251 donors in the system at the time this patient advisory was created. This is the most important variable impacting your chance of in the start-up phase, unexpected finding a match in the system. There are three strategies related to antibodies avoids you can employ to find a match in the system. cross match failures were disrupting a. You can continue to wait for new donors to enter the system that are compatible to you. This approach is generally used when patients are doing well on dialysis more than half of the match offers or are not yet on dialysis and do not have a problem waiting for a match. b. You can work with your transplant center to determine if any of the avoids listed being made. In May 2009, the virtual in the system have dropped in intensity and can be removed from your profile. cross match accuracy rate was 43%. Antibodies change over time so they should be measured and updated every three months. At that time, a national lab director c. If your center has the expertise to provide desensitization services, you should speak with them to see if you are a candidate for combining desensitization with group was formed by the leading paired exchange. 2. Relax Preference Restrictions: Because you have a significant number of antibody NKR centers to improve virtual cross avoids (35) listed in the system, you may need to be less restrictive in setting your match accuracy. By the end of 2011, preferences in order to increase your chance of finding a match. At the time this patient advisory was created, your recipient preferences were blocking 0% of the 4 biologically the virtual cross match accuracy rate compatible donors in the system. The table below shows your current preferences as well as the least restrictive preferences that will maximize your odds of finding a match. had increased to 94% increasing Preference Current Setting Less Restrictive Preferences Maximum Donor Age 70 70 the number of matches that actually

Minimum Donor Weight 0 0 NATIONAL KIDNEY REGISTRY (Mkgsinim) um HLA Match Points 0 0 made it to successful transplantation. Accept Shipped Kidney Yes Yes You currently have 1 donor(s) with the characteristics below: This dramatic improvement (Fig. Figure3. I6.mpro Swapve Donor Expert. Power: Donor Alias Age Weight (KGs) Blood Type (Type A Sub-Type) Work Up? GFR 7) has greatly accelerated the rate MORE ~55 86 B Not Applicable Yes 150 100%If you have additional donors that are not listed above, you shou94%ld have them worked up by of paired exchange transplantation your transplant center and entered into91% the system. If you are fortunate enough to have more 90%than one donor that is not listed above and is willing to participate in a swap, yandou shou isld the direct result of the collaboration of many prioritize these additional donor workups according to their power in paired exchange. By far, 80%the m ost powerful donors are O blood types. Any O donors should be workedexperienced up first for and skilled lab directors from leading 70%entry into paired exchange. The least powerful paired donors are AB blood types and should be worked up last. Donors under the age of 50 are slightly less powerful than 50NKR 65 yea centers.r old Key innovations that have improved 60%dono rs. Donors heavier than 80 KGs are slightly more powerful than donors wtheeigh ingprocess less include: than 80 KGs. If additional donors are entered into the system, it will expedite the process of 50%finding a better matched donor. 43% • Standardization of all antigen and antibody 40% codes VMX Accuracy 30%Monda y, December 26, 2011 • ReviewPage 1 of 1 of all cross match failures by 20% participating laboratory directors 10% • Corrective action plans for centers failing cross 0% matches 10/08 - 5/09 10/09 - 9/10 3/11-10/11 • Required entry of HLA-DP antibodies and HLA- Figure 7. Improved Virtual Cross Match DP donor antigens Accuracy. As the virtual cross match accuracy increased, 90% driven by the innovations adopted by the national 78% 80% lab director team, it became feasible to make larger 70% match offers. As a result, in 2010 NKR’s matching 60% 54% system was upgraded to find clusters up to 12 deep 50% so that large match offers could be made. Table 40% 2 and Figure 8 demonstrate the importance that 28% 30% virtual cross match accuracy has on the probability 20% Probability of Success of a 12-deep match offer actually working. Since the 10% implementation of 12-deep matching capabilities, 0% VMX @ 90% VMX @ 95% VMX @ 98% several 12-deep chains have actually gone from offer to completion. As a result of the success with Figure 8. Increasing probability of success by 12 deep chains, the NKR matching system was VXM accuracy. 260 VEALE AND HIL

Table 2. Probability of Success with 12-deep. Creation of the children and high PRA VMX Cumm VMX Cumm VMX Cumm program (CHIP) Position at 90% VMX at 95% VMX at 98% VMX 1 90% 90% 95% 95% 98% 98% Several members of the NKR Medical 2 90% 81% 95% 90% 98% 96% Board pointed out in 2010 that the NKR 3 90% 73% 95% 86% 98% 94% matching system could be utilized to get 4 90% 66% 95% 81% 98% 92% patients transplanted who do not have donors 5 90% 59% 95% 77% 98% 90% and who also have a low probability to receive 6 90% 53% 95% 74% 98% 89% a deceased donor transplant because they 7 90% 48% 95% 70% 98% 87% are very highly sensitized. By sharing bridge 8 90% 43% 95% 66% 98% 85% donors and non-directed donors across the 9 90% 39% 95% 63% 98% 83% NKR network, the process has improved the 10 90% 35% 95% 60% 98% 82% odds of finding a match for these hard-to-match 11 90% 31% 95% 57% 98% 80% patients without donors. Later in the testing of 12 90% 28% 95% 54% 98% 78% the program, the NKR Medical Board voted to enhanced to go 20-deep at the end of 2010 and include pediatric candidates in the program. further enhanced in 2011 with no depth limitations. The program was subsequently named the CHIP (Children and High PRA) program. Table 3 outlines Shipping living donor kidneys the CHIP program parameters. In 2011, the CHIP program facilitated transplants for 43 patients Shipping living donor kidneys was an including 4 children. unsettling prospect to many transplant clinicians. The perceived association between prolonged Standard financial model between centers cold ischemic time and poorer graft function, which has incorrectly been considered the defining One of the underappreciated barriers to difference between living and deceased donor paired exchange transplantation was the payment kidneys (5), caused some physicians to move process between transplant centers. An efficient cautiously. Lacking a strong bias and with the payment process is necessary so that the donor flexibility in the start times of chain transplants, centers can recover their costs for providing donor shipping living donor kidneys was the model that surgical services. This barrier became a crisis in the donors and recipients preferred and expressed late 2009 when an NKR-facilitated triple exchange via the NKR preferences. The willingness to ship was cancelled a day prior to surgery because the living donor kidneys expanded the options for pairs transplant centers involved could not agree on how as it broadened the geographic area from which much to pay each other. Not only were 3 patients compatible donors and recipients could participate. left on dialysis, but this last minute cancellation was In 2011 NKR centers shipped more than 100 living the catalyst for a broken chain as the bridge donor donor kidneys, sometimes from coast to coast. Many had cold ischemia Table 3. Children & High PRA (CHIP) Program. The CHIP times of more than 14 hours (6). A program helps patients without donors who are either children or are disadvantaged because they are sensitized. recent compilation of the outcomes for • NKR member centers with net chains started >0 may enroll up to 30 56 shipped living donor kidneys from candidates in the CHIP program. 30 centers, including many shipped • Net chains started is the total number of chains that a center starts by NKR centers, showed good early less the total number of chains a center ends. • CHIP candidates must be children (18 or younger) or sensitized function despite longer cold ischemia, adults. and attests to the safety and feasibility • The most likely blood types to find a CHIP match are “AB”, “A” and of the practice (7). “B” blood types. • The CHIP program is used as a last resort. The probability of a match dramatically improves when a paired donor(s) is available. 261 for this cluster eventually withdrew. In the wake of this devastating situation, the leading NKR member centers came together and developed a standard financial model that has eliminated nearly all of the problems related to payments between centers in NKR facilitated exchanges.

Streamlined regulatory compliance

In 2011 CMS issued new guidelines for living donor services which required centers participating in swaps to have written agreements between hospitals for living donor services. Since the NKR Figure 9. Regulatory Compliance. centers were already using a standard financial The average of the actual wait times of patients model, all that was needed was an additional transplanted during the year compliance section. The revised executed CMS (wait time = transplant date - enrollment date) compliant agreements are posted to the NKR web site with other required compliance information 6.0 NATIONAL KIDNEY REGISTRY 5.2 5.3 5.0 (already resident in the NKR database) providing 5 the basis for the automated process for regulatory compliance (Fig. 9). Months

RESULTS

The innovations pioneered by the National 0 2008 2009 2010 2011 kidney Registry and its Medical Board have surpassed all prior paired exchange efforts as Figure 10. Transplanted patient average wait time. measured by performance metrics covering areas including patient wait time, program matching Ending unmatched patient pool/annual transplant run rate efficiency, and the ability to get highly sensitized 3.8 patients matched and transplanted.

Patient wait time 2.0

Nothing is more important to a patient Years 0.9 1.1 undergoing dialysis than the expected wait time for a transplant. This is the most important performance measure for paired exchange programs. There are 2 fundamental methods for calculating paired 2008 2009 2010 2011 exchange wait time: 1) transplanted patient wait Figure 11. Enrolled patient projected wait time. time and 2) enrolled patient wait time (Figs. 10,11). pool size (inventory) by the annual exchange Transplanted patient wait time is the actual wait transplant run rate (usage). For example, if the pool time for those patients who have been transplanted. size is 200 and the transplant run rate is 100 then Enrolled patient wait time is not an exact measure an enrolled patient will wait an average of 2 years because it is unknown when an enrolled patient to get transplanted. will be transplanted. However this metric can Obviously pairs have very different actual wait be estimated using a calculation barrowed from times for getting matched and transplanted as modern inventory control theory by dividing the 262 VEALE AND HIL

Table 4. NKR Expected Months Wait Time. Patient Donor cPRA cPRA cPRA cPRA cPRA Blood Type Blood Type 0% 1-50% 51-80% 81-95% >95% O No Data No Data No Data 2 15 AB B No Data No Data No Data No Data No Data (Easiest) A 1 No Data 5 No Data No Data AB No Data No Data No Data 3 18 O 2 3 3 3 23 B 4 2 8 2 10 A A No Data 4 14 3 17 AB 2 No Data No Data No Data 54 O 4 No Data 7 72 16 B No Data 1 No Data 6 No Data B A 5 3 5 15 No Data AB 4 No Data No Data No Data No Data O 3 4 5 7 84 O B 7 30 No Data No Data No Data (Hardest) A 12 12 12 40 350 AB 70 No Data No Data 8 No Data depicted in Table 4, which shows the forecasted Program matching efficiency wait time for each blood type combination and cPRA category, but enrolled patients wait time is Measures of exchange program matching very helpful in evaluating the overall efficiency of efficiency include the percent of the pool that has the pool. been transplanted - the higher this percentage, Additional informative wait time metrics include the better. Figures 14 and 15 show the percent of the percent of transplants completed in less than pool measures by year with a breakdown of the six months (Fig. 12) and the forecasted wait time cumulative NKR pool at the end of 2011. for various pair blood type combinations and patient Matching highly sensitized patients cPRAs (Fig. 13). One of the key measures of paired exchange performance is the ability to match and transplant 89% of transplanted patients waited < 12 months highly sensitized patients. It is these highly

<6 Months 1.4% Number of transplants facilitated in <6 months / Total transplants for same year 6-12 Months 9.9% 1-2 Years 80% 75.0% 75.2% 70.5% 2+ Years 70% 13.5% 60% 50% 40% 30% 20% 75.2% 10% 0% 2009 2010 2011 Figure 13. Percent of patients transplanted Figure 12. 2011 transplants by wait time. within 6 months. 263

Total transplants per program to date / the actual number of matches using the NKR donor (total transplants + ending unmatched patients) pool and the actual avoids entered in the recipient 70% records. This cPRA calculation co-varies with the 64% 66% 60% standard UNOS cPRA but is sometimes higher

50% since the UNOS cPRA calculation does not reflect the additional antibodies (HLA-Cw, -DP) tracked in 40% 40% the NKR system. 30% 21% During 2011, the NKR witnessed an 20% unprecedented increase in the number of highly 10% sensitized patients that were successfully matched 0% and transplanted accompanied with an increase 2008 2009 2010 2011 in the percent of highly sensitized patients in the Figure 14. Cumulative pool transplanted by year. pool (Figs. 18, 19). Going forward, this dynamic is As of 12/31/2011 expected to continue as the pool size increases, 3% driven by hard-to-match patients, which will 6% increase the size of the donor pool, facilitating more transplants for the highly sensitized patients. Transplanted NATIONAL KIDNEY REGISTRY Pending 23% Bridge Donor withdrawal Unmatched <1 yr Unmatched 1-2 yrs There has been much debate about whether bridge donors can be trusted to pass on the Unmatched 2+ yrs 62% generosity and donate to the next recipient in the 6% chain after their intended recipient has already received a kidney transplant. A number of strategies have been adopted to streamline transplantation of Figure 15. Cumulative pool distribution by status. bridge donors and to avoid prolonged waits before sensitized patients that accumulate in paired donation (Table 5). Based on NKR observations exchange systems because they are the hardest of nearly 400 exchange transplants, bridge donor to match. Two metrics that show the matching withdrawals have declined as a percentage of performance of the NKR system for these hard to bridge donors each year (Table 6). The reasons for match patients are shown in Figures 16 and 17. The bridge donor withdrawals were not given for 2 of cPRA calculation used in these metrics is based on the 3 that occurred in 2008 and the third withdrew

45% 40.3% 40% cPRA 39% 34.5% 35% 51% 0% 60% 30% 0-50% 25.9% 90% 25% 50-80% 17% 20% 80-95% 10% 15% 15% >95% 13% 15% Average % CPRA 10% 8% 12% 17% 5% 4.1% 5% 11% 0%5% 8% 12% 11% 0% 0% 2008 2009 2010 2011 2008 2009 2010 2011 Figure 16. Average cPRA of transplanted Figure 17. Transplanted patients by year by patients by year. cPRA. 264 VEALE AND HIL

28% of transplanted patients >80% cPRA Table 5. Strategies to Eliminate Broken Chains. • Utilize larger clusters/ longer chains cPRA 11% • Transplant clusters simultaneously 0% • Pre-approve bridge donor candidates 0-50% • Only hold O donors as bridge donors 50-80% 17% 39% • End A, B and AB donors to the list 80-95% • Don’t allow bridge donors to wait too long • Avoid excessive bridge donor blood draws >95% • Complete full bridge donor medical evaluations • Avoid canceling swaps at the last minute

Table 6. Bridge Donor Withdrawals. 15% # Bridge # % Year Donors Withdrawn Withdrawn 17% 2008 9 3 33% 2009 29 2 7% Figure 18. 2011 transplants by cPRA. 2010 61 2 3% cPRA As of 12/31/2011 2011 75 0 0% 0% Total Bridge 174 7 0-50% Donors 50-80% guidelines. At a minimum, centers starting chains 80-95% >95% must fully disclose to non-directed donors all of 20% the potential donation options. Additionally, there 3% must be transparency in all aspects of paired exchange including governance, results reporting, 6% the unnecessary utilization of desensitization and 63% 8% center “hold backs” that are hurting patients.

Governance

In 2011 the NKR enhanced its bylaws to formalize the role of the Medical Board to control Figure 19. 2011 pool composition by cPRA. all medical policies through majority vote of the because of a long wait, multiple crossmatch failures Board. Six committees were formed to oversee the and job issues, In 2009 two donors withdrew, one key areas of expertise critical to paired exchange because of a prolonged wait to donate and the success. These key areas also benefit from second for medical reasons. Both withdrawals in consensus decisions among Member Centers. 2010 were due to medical concerns. By 2011 the Medical Board meetings are held periodically bridge donor withdrawal rate had dropped to zero. with formal voting on all significant medical policy Figure 20 shows how 6 of these 7 bridge donor changes or additions (e.g. match offer selection withdrawals affected transplant chains greater than policy). Figure 21 shows a snapshot of the NKR 1 deep. Medical Board at the end of 2011.

ETHICAL CONSIDERATIONS Transparency

With the growth of living donor transplants Transparency for paired exchange programs and particularly chains where donors are allocated has been a challenge because accurate to patients they do not know, there is a need for performance reporting requires a comprehensive the transplant community to establish some database and complex data presentation tools. 265

30 Active Chain Ended to List Broken 25

15 Length

5 NATIONAL KIDNEY REGISTRY

0 **Only 6 of 7 broken chains displayed due to exclusion of one deep chains.

Figure 20. Effect of bridge donor withdrawal on chain lengths.

National Kidney Registry Medical Board Revised 12/13/2011

Yolanda Becker, MD Howard Gebel, PhD Suzanne McGuire, RN David Serur, MD Michael Cecka, PhD Pam Heckathorn Hale Marc Melcher, MD, PhD Helen Spicer, RN Marian Charlton, RN Valerie Johnson, MD, PhD John Milner, MD Angela Stimpson Gabriel Danovitch, MD Sandip Kapur, MD Marie Morgievich, ANP Barry Straube, MD Michael Dattoli, MD Steven Katznelson, MD John Roberts, MD Jeffrey Veale, MD Connie Davis, MD Debbie Mast Sally Satel, MD

Surgery Nephrology Histo Research Operations Finance & Admin Chair & Surgical Chair & Medical Chair & Lab Chair & Research Chair & Paired Exchange Co-chairs Director Director Director Director Director Debbie Mast & David Serur, MD Michael Cecka, PhD Jeffrey Veale, MD Marc Melcher, MD Marian Charlton, RN Gigi Spicer, RN

Barry Browne, MD Tony Bonagura, MD LeeAnn Baxter-Lowe, PhD LeeAnn Baxter-Lowe, PhD Janine Sabetto-Castillo, RN Angie Korsun Luis Fernandez, MD Shlomo Cohney, MD Darshana Dadhania, MD Connie Davis, MD Diane James, RN Andrea Tietjen Sandi Kapur, MD Gabe Danovitch, MD Nick DiPaolo, PhD Malek Kamoun, MD Paula Mark, RN Kari Jones John Milner, MD Connie Davis, MD Malek Kamoun, MD, PhD David Leeser, MD Suzanne McGuire, RN Ursula Lebron-Banks John Roberts, MD Fuad Shihab, MD John Lunz, PhD John Milner, MD Marie Morgievich, RN Bill Vaughan Chris Troppmann, MD Christine Wu, MD Paul Warner, PhD Jeffrey Veale, MD Dianne la Pointe-Rudow, NP Henrie Tan, MD Tammy Wright, RN

Figure 21. National Kidney Registry Medical Board. 266 VEALE AND HIL

NKR is setting the standard for transparency by Utility vs Justice communicating results on a quarterly basis to the transplant community. Many of the results that are Candidates on the deceased donor waiting reported by NKR quarterly are also presented in list collectively benefit when non-directed living the Results section of this chapter. donor organs are allocated to initiate chains. Living Additional transparency is needed to manage donors are liberated throughout a chain, removing the unnecessary “promotion” of desensitization patients from the wait list. Without chains these when paired exchange can be employed to find living donors would never have been utilized due a clean match, which leads to better patient to incompatibility. This net gain of living donors outcomes. In some cases, paired exchange reduces the competition for deceased donors programs inappropriately combine desensitization for those candidates on the waiting list allowing with paired exchange because their donor pool other patients to move up the wait list and take the is too small. This is not in the best interest of the place of the recipients on the wait list that received patient when a good match that does not require a kidney from a living donor in a chain. The desensitization can be found in a larger pool such resulting multiplier effect is powerful. For example, as the NKR. if one donor starts a chain that is closed after 6 Single center “hold backs” are also delaying transplants, 5 recipients are removed from the transplants and forcing poor matches when wait list when they receive a living donor transplant transplant centers attempt to keep exchanges and one recipient on the wait list receives a kidney “in-house”. This practice is evident at a handful of directly from the last living donor in the chain. centers in the U.S. and puts the patient’s interests in conflict with the transplant center’s interest. FUTURE DIRECTIONS Single center swaps rarely move faster or find The future of paired exchange is one of rapid better matches than those organized by national growth. This will be driven by transplant center programs such as the NKR because of the limited outreach efforts that are educating the 80,000+ size of the single center donor pool and the lack patients on the wait list, including thousands that of sophisticated software utilized in single center have incompatible donors. An increasing number of swaps. Organizing single center swaps does have patients with compatible donors are also entering some advantages as they are logistically simpler swaps to improve their match while helping other and slightly more profitable because they eliminate patients with incompatible donors get transplanted. costs related to shipping and matching. By the end of the decade, the current practice of NDD allocation and coercion living donors giving their kidney to a friend or family member may be a relic of the past (except for well- Social concerns for NDDs include their matched siblings/relatives) with most donors giving motivation, possible hidden compensation and their kidney to a stranger in a chain so that all psychiatric history to name a few. Our experience recipients get better matched donors, allowing the indicates that only 1% of inquiring NDD candidates transplanted kidneys to last longer. The increased make it all the way through the evaluation process to volume in paired exchange will set the stage to actual donation. In addition to appropriate medical match many more patients and greatly expand and psychological screening, other ethical issues the donor pool. This will facilitate transplants for exist. Should the kidney be allocated to the center’s thousands of additional patients, saving the US deceased donor list, 6-antigen match national list, health care system billions in dialysis-related costs. a child, or to start a chain? These questions can Compatible pairs only be answered by the donor, so it is important that donors know all the options before they decide Many medical professionals and their patients when and where to donate. are beginning to realize that compatible pairs 267 can improve their donor recipient match and Table 7. Insurance Company Savings for each improve the patient’s outcome by participating exchange transplant. in an exchange (10,11). These benefits are most Annual Dialysis Costs * $150,000 pronounced for compatible pairs comprising an Years on Dialysis X 3 O donor and unsensitized non-O patient, since Dialysis Savings $450,000 there are shortages of O donors in all exchange Cost of Transplant ($100,000) programs. Improved matches are usually evaluated Post-Transplant Costs ($50,000) on 3 dimensions; donor age, HLA match and Net Savings $300,000 donor size. Although the improvements in patient * Pittsburg Inquirer 9/28/09 – does not include other dialysis related costs outcomes are well documented related to donor age and HLA match, there is limited research to Table 8. Medicare Savings for each exchange demonstrate donor size improves graft survival or transplant. half-life (12). In addition to finding a better matched Dialysis Less Transplant Maintenance (GAO study) $42,388 donor and potentially achieving a better outcome, Disability & Lost Tax Revenue (NKR the compatible pair will typically facilitate many White Paper) $18,500 more transplantations by filling a missing gap in the Total Annual Savings $60,888 chain and increasing the liquidity of the pool. Average Kidney Life Years * X 20 NATIONAL KIDNEY REGISTRY $1,217,760 Economic benefits of paired Approximate Cost of Transplant ($100,000) exchange transplantation Present Value of Savings (assumes inflation is roughly equal to $1,117,760 The economic benefits of paired exchange to the U.S. government cost of capital) the US health care system over the next decade * Does not include additional kidney life years from compatible pairs who achieve better compatibility may be in excess of $100 billion dollars. When through paired exchange. ESRD patients are removed from dialysis through paired exchange commensurate with their financial paired exchange transplantation, an enormous gain, many more of their customers/members will economic savings accrues. There are 3 primary receive transplants. financial beneficiaries of a paired exchange transplant 1) transplant centers 2) insurance Combining desensitization with companies and their self-insured customers and 3) chains Medicare and the US government. When a paired exchange transplant takes place, the transplant Transplant teams specializing in desensitization center/hospital realizes approximately $90,000 often see the rapid growth of chain transplantations - $200,000 in incremental revenue. If the patient as a threat to their clinical workload. Likewise, is covered by private insurance, the insurance proponents of exchanges often point out the added company saves about $300,000 (Table 7) based expense ($28,979 / transplant) and immune- on figures provided by the largest health insurance mediated injury associated with desensitization companies in the United States. Finally Medicare (13). However, these 2 approaches are not mutually and the US government save approximately exclusive and are actuality quite complementary. $1,100,000 per patient transplanted, mostly by With access to desensitization and chain matching, avoiding ongoing dialysis costs (Table 8). To date, a center can essentially stack the deck in favor of neither the insurance industry nor Medicare has the patient. For example, a potential recipient who provided any material financial support to paired has multiple HLA antibodies, some of which are exchange efforts with most of the funding coming stronger and others that are weaker. When this from charitable contributions and transplant pair is placed into a registry, the weaker antibodies centers. When Medicare and the insurance industry that are removed through desensitization can be begin providing financial contributions to support ignored in the matching process. In this case, the 268 VEALE AND HIL center would not list these weak antibodies for this of removing one or more unacceptable antigens patient and the patient could receive a transplant on the matchability (i.e. pair match power) of their through a chain in combination with desensitization. registered pairs. This allows Member Centers to The combination of paired exchange and understand in advance the potential impact that desensitization is often the best modality of highly combining desensitization with paired exchange sensitized patents. The NKR has added a “toolbox” will have on the probability of finding a match and to the website that allows centers to see the effects the expected wait time for an exchange transplant. NKR Program Statistics. 2008 2009 2010 2011 1 Transplants Facilitated 21 62 131 175 2 Ending Unmatched Patient Pool 80 127 120 201 3 Cumulative Transplants 21 83 214 389 4 Cumulative Patient Pool 101 210 334 590 5 Percent of Pool Transplanted 21% 40% 64% 66% 6 Enrolled Patient Average Wait Time 3.8 2.0 0.9 1.1 7 Transplanted Patient Average Wait Time 5.1 5.3 6.0 5.0 8 Average cPRA of Transplanted Patients 4.1% 25.9% 34.5% 40.3% 9 Number of Transplants Completed by cPRA 10 >95% 0 5 16 20 11 80-95% 1 7 16 29 12 50-80% 0 5 19 27 13 0-50% 1 8 13 30 13 0% 19 37 67 69 14 Sub-total 21 62 131 175 15 Percent of Transplants Completed by cPRA 16 >95% 0% 8% 12% 11% 17 80-95% 5% 11% 12% 17% 18 50-80% 0% 8% 15% 15% 19 0-50% 5% 13% 10% 17% 20 0% 90% 60% 51% 39% 21 Sub-total 100% 100% 100% 100% 22 Number of Transplanted Patients with cPRA >80% 1 12 32 49 23 Percent of Transplanted Patients with cPRA >80% 5% 19% 24% 28% 24 Number of Unmatched Patients by cPRA at year-end 25 >95% 152 26 80-95% 15 27 50-80% 14 28 0-50% 14 29 0% 50 30 Sub-total 245 31 Percent of Unmatched Patients by cPRA at year-end 32 >95% 62% 33 80-95% 6% 34 50-80% 6% 35 0-50% 6% 36 0% 20% 269

NKR Program Statistics, cont'd. 2008 2009 2010 2011 37 Sub-total 100% 38 Number of Transplants Completed by Wait Time 39 < 6 months 21 42 74 106 40 6-12 months 0 10 14 19 41 1-2 years 0 4 15 14 42 2+ years 0 0 2 2 43 Sub-total 21 56 105 141 44 Percent of Transplants Completed by Wait Time 45 < 6 months 100.0% 75.0% 70.5% 75.2% 46 6-12 months 0.0% 17.9% 13.3% 13.5% 47 1-2 years 0.0% 7.1% 14.3% 9.9% 48 2+ years 0.0% 0.0% 1.9% 1.4% 49 Sub-total 100% 100% 100% 100% 50 Total Chains Started 3 8 28 38 51 Total Loops Completed 0 3 2 3 NATIONAL KIDNEY REGISTRY 53 Number of broken chains 3 2 2 0 54 Bridge donors held 9 29 61 75 55 Percent of broken chains 33% 7% 3% 0% THE NEW YORK TIMES ARTICLE donated blood, but the story so captivated him "60 LIVES, 30 KIDNEYS, ALL that two days later he called Riverside Community LINKED" Hospital to ask how he might do the same thing. Halfway across the country, in Joliet, Ill., Donald The following New York Times article describes C. Terry Jr. needed a kidney in the worst way. one of the longest living donor chains to date. The Since receiving a diagnosis of diabetes-related editors of Clinical Transplants thank Joe Sinacore renal disease in his mid-40s, he had endured the at National Kidney Registry for acquiring the burning and bloating and dismal tedium of dialysis copyrights from The New York Times and making it for nearly a year. With nobody in his family willing possible for us to include this extraordinary article or able to give him a kidney, his doctors warned in this book. that it might take five years to crawl up the waiting list for an organ from a deceased donor. Originally printed in The New York Times, February “It was like being sentenced to prison,” Mr. 18, 2012. Terry recalled, “like I had done something wrong in By Kevin Sack my life and this was the outcome.” RIVERSIDE, Calif. — Rick Ruzzamenti admits As a dawn chill broke over Chicago on Dec. to being a tad impulsive. He traded his Catholicism 20, Mr. Terry received a plump pink kidney in a for Buddhism in a revelatory flash. He married a transplant at Loyola University Medical Center. Vietnamese woman he had only just met. And then He did not get it from Mr. Ruzzamenti, at least a year ago, he decided in an instant to donate his not directly, but the two men will forever share a left kidney to a stranger. connection: they were the first and last patients In February 2011, the desk clerk at Mr. in the longest chain of kidney transplants ever Ruzzamenti’s yoga studio told him she had recently constructed, linking 30 people who were willing donated a kidney to an ailing friend she had bumped to give up an organ with 30 who might have died into at Target. Mr. Ruzzamenti, 44, had never even without one. 270 VEALE AND HIL

What made the domino chain of 60 operations Children donated for parents, husbands for possible was the willingness of a Good Samaritan, wives, sisters for brothers. A 26-year-old student Mr. Ruzzamenti, to give the initial kidney, expecting from Texas gave a kidney for a 44-year-old uncle nothing in return. Its momentum was then fueled in California whom he rarely saw. In San Francisco, by a mix of selflessness and self-interest among a 62-year-old survivor of Stage 4 Hodgkin’s donors who gave a kidney to a stranger after lymphoma donated for her son-in-law. learning they could not donate to a loved one On Aug. 15, Mr. Ruzzamenti’s kidney flew because of incompatible blood types or antibodies. east on a Continental red-eye from Los Angeles to Their loved ones, in turn, were offered compatible Newark and was rushed to Saint Barnabas Medical kidneys as part of the exchange. Center in Livingston, N.J. There it was stitched into Chain 124, as it was labeled by the nonprofit the abdomen of a 66-year-old man. National Kidney Registry, required lockstep The man’s niece, a 34-year-old nurse, had coordination over four months among 17 hospitals wanted to give him her kidney, but her Type A blood in 11 states. It was born of innovations in computer clashed with his Type O. So in exchange for Mr. matching, surgical technique and organ shipping, Ruzzamenti’s gift, she agreed to have her kidney as well as the determination of a Long Island shipped to the University of Wisconsin Hospital in businessman named Garet Hil, who was inspired Madison for Brooke R. Kitzman’s transplant. It was by his own daughter’s illness to supercharge the Ms. Kitzman’s former boyfriend, David Madosh, notion of “paying it forward.” who agreed to donate a kidney on her behalf Dr. Robert A. Montgomery, a pioneering despite their acrimonious split. transplant surgeon at Johns Hopkins Hospital, Mr. Madosh’s kidney flew to Pittsburgh for which was not involved in the chain, called it a Janna Daniels, a clerical supervisor, who got her “momentous feat” that demonstrated the potential transplant at Allegheny General Hospital. And her for kidney exchanges to transform the field. “We husband, Shaun, a mechanic, sent his kidney are realizing the dream of extending the miracle of to Mustafa Parks, a young father of two at Sharp transplantation to thousands of additional patients Memorial Hospital in San Diego. each year,” he said. On and on the chain extended, with kidneys The chain began with an algorithm and an flying from coast to coast, iced down in cardboard altruist. Over the months it fractured time and boxes equipped with GPS devices and stowed on again, suspending the fates of those down the line commercial aircraft. until Mr. Hil could repair the breach. Eventually, he In a system built on trust, one leap of faith succeeded in finding needle-in-a-haystack matches followed another. The burdens of scheduling for patients whose antibodies would have caused operations all across the country — so donors them to reject organs from most donors. would not have to travel — meant that operations Until now, few of the donors and recipients were not always simultaneous, or even sequential. have known one another’s names. But 59 of the 60 The most worrisome risk was that donors would participants consented to be identified by The New renege once their loved ones received kidneys. York Times and to tell the stories, each with distinct After John A. Clark of Sarasota, Fla., got a shadings, that ultimately connected them. transplant on Sept. 28 at Tampa General Hospital, Despite an intensely bitter breakup, a Michigan his wife, Rebecca, faced a 68-day wait before it man agreed to donate a kidney for his former was her turn to keep the chain going. Ms. Clark girlfriend for the sake of their 2-year-old daughter. said that it crossed her mind to back out, but that A woman from Toronto donated for her fifth cousin she swatted away the temptation. “I believe in from Bensonhurst, Brooklyn, after meeting him by karma,” Ms. Clark said, “and that would have been chance in Italy and then staying in touch mostly by some really bad karma. There was somebody out text messages. there who needed my kidney.” 271

An Organ to Spare Domino chains, which were first attempted in 2005 at Johns Hopkins, seek to increase the It is considered a quirk of evolution that humans number of people who can be helped by living have two kidneys when they need only one to filter donors. In 2010, chains and other forms of paired waste and remove excess fluid from the body. Yet exchanges resulted in 429 transplants. Computer when kidneys fail, whether from diabetes or high models suggest that an additional 2,000 to blood pressure or genetic disorders, they tend to 4,000 transplants could be achieved each year if fail in tandem. Americans knew more about such programs and if Death can arrive in a matter of weeks for there were a nationwide pool of all eligible donors many renal patients if they do not have their blood and recipients. cleansed through dialysis. The process takes Such transplants ultimately save money as well almost four hours, three times a week, and leaves as lives. The federal Medicare program, which pays many too drained to work. Only half of dialysis most treatment costs for chronic kidney disease, patients survive more than three years. saves an estimated $500,000 to $1 million each Many of the 400,000 Americans who are time a patient is removed from dialysis through tethered to dialysis dream of a transplant as their a live donor transplant (the operations typically pathway back to normal. But with the demand for cost $100,000 to $200,000). Coverage for kidney NATIONAL KIDNEY REGISTRY kidneys rising faster than the number of donors, disease costs the government more than $30 billion the waits have grown longer. While about 90,000 a year, about 6 percent of the Medicare budget. people are lined up for kidneys, fewer than 17,000 Dialysis, which in the United States is almost receive one each year, and about 4,500 die waiting, always administered in outpatient clinics, saps the according to the United Network for Organ Sharing, productivity of caregivers as well as of patients. which maintains the wait list for the government. Nearly two years ago, Kent Bowen, 47, of Austin, Only a third of transplanted kidneys come Tex., gave up his job hanging gutters, and much of from living donors, but they are coveted because his freedom, so he could provide dialysis at home they typically last longer than cadaver kidneys. to his mother, Mary Jane Wilson. For kidneys transplanted in 1999, 60 percent of Before donating a kidney for her as part of the organs from live donors were still functioning after chain on Dec. 7 at Methodist Hospital in Houston, 10 years, compared with 43 percent of organs from Mr. Bowen said he looked forward not only to deceased donors. helping his mother, but also to a long-deferred Although other living tissue can be transplanted fishing trip. — slices of pancreas, liver and intestine, bone “In all actuality,” he said, “giving a kidney is a marrow and lobes of lung — kidneys are uniquely small price to pay for getting my life back.” suited because donors have a spare and the operations are almost always successful. Understanding the Pain A reason there are not more live kidney donations, however, is that about a third of Garet Hil and his wife, Jan, may never fully transplant candidates with a willing donor find that recover from the snowy night in February 2007 they are immunologically incompatible. Some, when they took their 10-year-old daughter in because of previous transplants, blood transfusions with flu symptoms and emerged with a shocking or pregnancies, may have developed antibodies diagnosis of nephronophthisis, a genetic kidney- that make them highly likely to reject a new kidney. wasting disease. They could not imagine sacrificing Using a blood-filtering technique known as her youth to dialysis. plasmapheresis, doctors can now lower the odds Because Mr. Hil and his daughter shared that a recipient will reject an incompatible kidney. the same blood type, he assumed he would be But the procedures are taxing and expensive. able to give her one of his kidneys. But two days before surgery, doctors canceled the operations 272 VEALE AND HIL

reconnaissance ranger with an M.B.A. from the Wharton School, he had managed a series of data and logistics companies in Boston and New York and understood the worlds of both computing and finance. He had made his money and could step off the career track to give the registry his time and the resources of his software-consulting firm. He had a background in quantitative math and enough drive to plow through medical texts about organ compatibility. Over time, he led a team in designing sophisticated software that evolved to build ever- longer chains. Disney-hero handsome, with a cleft chin and thick wavy hair, Mr. Hil marketed his registry to hospitals with PowerPoints and passion. The transplant world initially regarded him as an THE FOUNDER: Garet Hil formed the National Kidney Registry after his daughter became ill. interloper. But he has now persuaded 58 of the country’s 236 kidney transplant centers, including after discovering that his daughter had developed many of the largest, to feed his database with antibodies that would most likely cause rejection. information about pairs of transplant candidates Jan Hil and six other family members and their incompatible donors. volunteered but were also ruled out. Mr. Hil and Starting at 5 a.m. each workday, Mr. Hil his daughter joined several of the registries that manipulates several hundred pairs into transplant had started to arrange kidney exchanges, but the chains with a few clicks of a mouse. Last year, he pools were small and they never found a match. arranged 175 transplants this way, including the Fortunately, one of Mr. Hil’s nephews then was 30 in Chain 124, more than any other registry. On tested and was able to donate. average, patients received transplants about a year After the successful transplant, Mr. Hil, a veteran after being listed. business executive, could not shake his frustration The same year that Mr. Hil’s daughter got sick, that a more effective registry for paired kidney Congress amended the National Organ Transplant donation did not exist. “The exchange systems out Act to clarify that paired exchanges do not violate there weren’t industrial strength,” he said. federal laws against selling organs. The blessing By the end of 2007, the Hils had formed the from Washington broke down resistance in many National Kidney Registry and rented office space hospitals just as the National Kidney Registry was in an old clapboard house in Babylon, N.Y. The opening for business. couple invested about $300,000 to start it, and Mr. Hil, who is now 49, ran the registry without a salary. The Evolving Chain “The goal was very simple: get everybody transplanted in under six months if you had a living Although the first live kidney was transplanted donor,” he said. “One of the things that drove us in 1954 in Boston, three decades passed before was the enormity of the problem. The other thing a Stony Brook University surgeon named Felix T. that drove us was that we understood the pain of Rapaport first theorized about kidney swaps ina being in that situation.” 1986 journal article. Korean surgeons completed Mr. Hil turned out to be the right person to the first exchanges in 1991, but they were not infuse the budding science of kidney exchange successfully attempted in the United States for with an entrepreneurial spark. A former Marine nearly another decade. 273

Simple swaps among two pairs, with the Chain 124 even included one pair that was operations performed at the same hospital on the immunologically compatible. Josephine Bonventre, same day, quickly evolved into complex exchanges a 40-year-old real estate agent from Toronto with among three pairs and then four and then six. Type O blood, could have donated a kidney directly Then in 2007, a transplant surgeon at the to her fifth cousin, Cesare Bonventre, a 27-year-old University of Toledo Medical Center, Dr. Michael tile worker from Brooklyn with Type B. A. Rees, had a forehead-slapping insight. If an But a second level of matching requires the exchange began with a Good Samaritan who synching of six antigens, a series of proteins that donated to a stranger, and if the operations did not determine compatibility. By joining the chain and have to be simultaneous, a chain could theoretically donating down the line, on Dec. 6 at NewYork- keep growing, limited only by the pool of available Presbyterian Hospital, Josephine enabled Cesare donors and recipients. Dr. Rees reported in to get a stronger match — three antigens instead of 2009 that he had strung together a chain of 10 one. Her donation as a valued Type O then set off transplants. the final 11 transplants. Mr. Hil seized on the idea and set out to build an The registry did not charge transplant centers algorithm that would enable even more transplants. for its services until 2010, when Mr. Hil imposed Nowadays, his pool typically consists of 200 to 350 fees to help cover costs. Hospitals now pay NATIONAL KIDNEY REGISTRY donor-recipient pairs. That is enough to generate membership dues and a charge of $3,000 per roughly a googol — 10 to the 100th power — of transplant that is reimbursed by many private possible chains of up to 20 transplants if all of the pairs are compatible, said Rich Marta, the registry’s senior software designer. The program quickly eliminates matches that will not work because of incompatible blood types or antibodies, or because a transplant candidate insists that a donor be under a certain age or a close immunological match. It then assembles up to a million viable combinations at a rate of 8,000 per second. The algorithm ranks the possible combinations by the number of transplants they would enable, LINKS IN THE CHAIN: Josephine Bonventre with weight given to chains that find kidneys for and Cesare Bonventre. hard-to-match patients and those who have waited a long time. There are several registries like Mr. Hil’s, each with a distinct approach. Largely unregulated by government, they invite sensitive questions about oversight and ethics, including how kidneys are allocated. A number of medical societies are convening in March to seek consensus on that and other issues related to paired exchanges. Mr. Hil knows the patients in his pool only by code names and leaves all personal interactions to the hospitals. He keeps several chains running at a time, and says tending to them is like playing A COUSIN’S GIFT: Josephine Bonventre’s three-dimensional chess. donation allowed her cousin to get a stronger match, and also set off the final 11 transplants. 274 VEALE AND HIL insurers but not by Medicare. The transplant The Initial Link recipients must be insured. Each year, the registry’s chains have grown Until recently, hospitals regularly turned longer, with Chain 124 topping the previous record away Good Samaritan donors on the working by seven transplants. “We’ve just scratched the assumption that they were unstable. That has surface,” said Mr. Hil, who wears gold kidney- changed somewhat with experience. But when Rick shaped cufflinks. Ruzzamenti showed up at Riverside Community Long transplant chains save more lives Hospital asking to give a kidney to anyone in than short chains. But they come with trade-offs need, he still underwent rounds of psychological because the longer they grow, the higher the risk screening as well as medical tests. that a donor will renege or that a link will break for The doctors and social workers did not know other reasons. what to make of Mr. Ruzzamenti at first. He had The record-breaking chain survived its share a flat affect and an arid wit, and did not openup of logistical setbacks. On Aug. 29, after the first right away. As the hospital’s transplant coordinator, five transplants, Mr. Hil lost a link because a donor Shannon White, pressed him about his motivations could not take the necessary two to four weeks and expectations, he explained that his decision away from work. Later that day, he lost another seemed rather obvious. when a transplant coordinator informed him that “People think it’s so odd that I’m donating a a potential recipient was an illegal immigrant and kidney,” Mr. Ruzzamenti told her. “I think it’s so odd therefore could not be covered by Medicare. that they think it’s so odd.” In late October, an entire segment fell apart The hospital wanted to make sure that he when a donor at California Pacific Medical Center was not expecting glory, or even gratitude. Mr. in San Francisco backed out for unexplained Ruzzamenti stressed that no one should mistake “personal reasons.” It was as if one domino had him for a saint. fallen short of the next, leaving those still standing He had, after all, been a heavy drinker in his frozen in place. youth and had caroused his way through the Navy. “This makes us all sick,” Dr. Steven Katznelson He could be an unsmiling presence at work, where e-mailed Mr. Hil. “We did not see this coming.” he helped manage a family electrical contracting “Wow,” Mr. Hil wrote back. The donor “just put business. He admitted that he did not visit his 23 patients at risk.” parents or grandmother enough. The dependency of each link on the others Despite his occasional surliness, Mr. kept patients on edge. “Things can happen,” Ruzzamenti said he felt driven to help others when Candice Ryan fretted a few days before her Dec. 5 possible. transplant at Massachusetts General Hospital. “You And as he considered the relative risks and just pray that everything goes well. I can’t relax until benefits of organ donation, particularly to relieve I’m asleep and on the table.” a whole chain of suffering, it just made so much Depending on the makeup of his registry at sense. “It causes a shift in the world,” he said. any moment, Mr. Hil likes to stretch his chains as Perhaps, he said, there was some influence long as reasonable and then end them if a donor is from a Tibetan meditation he had practiced when difficult to match or if one chain is draining others of he was first drawn to Buddhism six years ago. It is potential transplants. known as Tonglen. “You think of the pain someone’s He does so by arranging for the final kidney to in, and imagine you take it from them and give them go to a fortunate transplant candidate like Mr. Terry back good,” he said. who does not have a willing donor. Mr. Ruzzamenti said he was in a position to donate only because the economy had dried up so much of his work. He was essentially unemployed 275 and could take time off to recuperate. The 30 kidney On Aug. 31, Ms. Duke received a kidney from a recipients, he observed dryly, could “all thank the woman in California and Mr. Person sent his to Ohio. recession.” As they recuperated at NewYork-Presbyterian, Mr. When Mr. Ruzzamenti told his wife, My Person found himself regularly hobbling down to Nhanh, about his plans, she made it abundantly her room. Once they were both back on their feet, clear, despite her rudimentary English, that they started dating more regularly. she would leave him and return to Vietnam if he “I’ve never had any person in my life actually followed through. She had immigrated only eight do what they say they’re going to do,” Ms. Duke months before, after a marriage largely arranged said, “especially men. It spoke volumes that he was by the Buddhist temple where Mr. Ruzzamenti a man of his word.” volunteered as a groundskeeper. If he died on the It was a different kind of devotion that led David table, she demanded, how would she get by in a Madosh, 47, to donate a kidney for Brooke country where she felt so out of place? Kitzman, 30. Their four-year relationship, “I wanted to scare him,” Ms. Ruzzamenti, who is which had produced a 2-year-old daughter, soured known as Lucy, said as she combed her husband’s just as he was getting tested as a potential donor. close-cropped hair with her fingers. “And to tell him The breakup, caused partly by the strains of her that it scares me.” illness, was ugly enough that when Ms. Kitzman NATIONAL KIDNEY REGISTRY Mr. Ruzzamenti was impressed by his petite later matched to become part of the chain, she put wife’s ferocity — “She’s a bully,” he said — but he the odds at no better than 50-50 that Mr. Madosh disregarded her threat. He knew research showed would still donate. that the risk of death from kidney retrieval surgery But Mr. Madosh, who lost his mother when he was 3 in 10,000 and that people with one kidney live was 5, did not want his daughter, Elsie, to lose hers. as long as those with two. To him, there was little The youngest of 12 children, he said he had doubt that any good he created would far outweigh been passed from one foster home to the next, any temporary discomfort to him or his wife. eight in all, some that he described as little more As it happened, Mr. Ruzzamenti experienced than labor camps. “I don’t want my daughter to an unusual level of pain during his recuperation at have to experience that,” said Mr. Madosh, a tree Riverside. It sometimes left him balled up in agony, cutter by trade. “No matter what it takes, a daughter and the Demerol only made him hallucinate. needs her mother.” He did not really want company. But when the Ms. Kitzman said she was grateful for Mr. pain stirred him awake at night, he could see Lucy Madosh’s kidney, and had told him so when they sleeping in the hospital bed beside his. visited in a hospital corridor. But both made it clear that his act of charity had barely eased the tension Acts of Devotion between them. Mr. Madosh said he took satisfaction enough There were other love stories along the way. from seeing Elsie at play with her re-energized Gregory Person and Zenovia Duke, both now 38, mother. “When her mama comes to get her, and had been junior high prom dates in 1987 in Astoria, she gives her hugs and kisses, that’s it right there,” Queens. They lost touch and then reconnected on he said. Facebook after each had divorced. They saw each other occasionally, but he lived in Queens and she A Wish Come True near Albany, so the relationship never got serious. Not long after they reconnected, Mr. Person’s On Dec. 19, Chain 124 hurtled toward its half-sister died of kidney failure and he pledged to conclusion with a final flurry of procedures at help someone else beat the disease if ever given Ronald Reagan U.C.L.A. Medical Center in Los the chance. Then Ms. Duke learned she needed a Angeles. Between dawn and dusk, three kidneys transplant. were removed and three were transplanted in 276 VEALE AND HIL neighboring operating rooms. One flew in from San In his hospital room before surgery, with seven Francisco. The last took off for O’Hare. family members shoehorned into every nook, Mr. At the end of the cluster were Keith Zimmerman, Zimmerman calmed his nerves by listening to Aaron 53, a bearish, good-humored man with a billygoat’s Neville on his iPod. He said he considered himself beard, and his older sister, Sherry Gluchowski, 59. “the lottery winner” in the chain because his kidney She had recently moved from California to Texas would be coming from a healthy 28-year-old, Conor but returned to donate her kidney. Bidelspach of Bend, Ore. The siblings had always been close, although The surgery to remove a kidney, known as a family members marveled at their ability to bicker nephrectomy, is remarkably bloodless these days. for 15 minutes over the proper way to construct With Mr. Bidelspach on the table, Dr. Peter G. a peanut butter sandwich. Their mother, Elsa Schulam cut four dime-sized incisions on the left Rickards, remembered teaching them as children side of the abdomen. Through tubes inserted in the “that they might not have their mommy and daddy openings, the surgeon and his team maneuvered all the time, but they will always have each other.” their cauterizing scalpels and a laparoscopic Mr. Zimmerman, who runs a repossession camera, which relayed images of Mr. Bidelspach’s firm with his wife in Santa Clarita, had been given insides to monitors overhead. a diagnosis of kidney disease 25 years ago. With The scalpel’s super-heated pincers clamped the help of a nutritionist, he had managed to avoid down like crab claws, searing the kidney from dialysis until the very last day before his transplant, surrounding tissue. There was no need to cut any when his doctor said the procedure was needed to muscle. clear his body of excess fluid.

FROM START TO FINISH: A donation by a Good Samaritan, Rick Ruzzamenti, upper left, set in motion a 60-person chain of transplants that ended with a kidney for Donald C. Terry Jr., bottom right. 277

Once the kidney was free of connective tissue, Dr. Schulam clamped and snipped the renal artery and vein and ureter. He captured the kidney in a plastic bag, cinched it shut, and withdrew it quickly through a finger-length incision along the pelvic line. The doctor poured the kidney into a bowl of ice and drained it of remaining blood. The slush in the blue bowl turned fruit-punch pink. As others stitched up Mr. Bidelspach, Dr. Schulam wheeled the kidney on a cart into an adjoining operating room, where Mr. Zimmerman was already anesthetized. After stretching a hole in IN TRANSIT: A courier, Cynthia Goff, saw that Mr. Zimmerman’s midsection with a metal retractor, the kidney donated by Sherry Gluchowski in Dr. Jeffrey L. Veale lowered the kidney into place Los Angeles got to its recipient in Chicago. and sewed in the renal artery and vein. As soon store selling Elmo dolls for Christmas. Escorted as he unclamped them, the kidney pinked up onto United 564, an overnight flight that would land with blood flow. Before attaching the ureter to the in Chicago at 5 a.m., she stowed the box in the NATIONAL KIDNEY REGISTRY bladder, he gently massaged the tip of the narrow business-class closet, next to a flight attendant’s tube between two fingers and watched it spurt a overcoat. few drops of urine. Airplanes carrying donor organs are granted “No more dialysis for Mr. Zimmerman,” Dr. special status, allowing them to move to the front Veale declared. “This total stranger’s kidney is of takeoff lines and ahead of air traffic. Mr. Hil, making him pee.” He left Mr. Zimmerman’s own who tries to avoid routing kidneys on connecting kidneys to shrivel harmlessly in place (removing flights and always schedules backups, said none them would add to surgical risk). of his registry’s transplants had been held up by Meanwhile, Dr. Schulam was in yet another transportation problems. operating room removing Ms. Gluchowski’s kidney. By the time Ms. Gluchowski’s kidney made it to He placed it in a plastic bag filled with a Loyola and was transplanted into Mr. Terry, it had preservative solution and knotted it shut, like a been cold for almost 12 hours. Early studies have goldfish brought home from the pet store. It was found no evidence that shipping live kidneys such packed in a plastic tub, topped with ice, and distances affects their immediate function. loaded into a cardboard box marked “Left Kidney Chain 124 ended at Loyola because Mr. Hil — Donated Human Organ/Tissue for Transplant — had arranged for the final kidney to go to a hospital Keep Upright.” that had produced a Good Samaritan donor to start A courier in one of Quick International’s big red a chain in the past, thus closing a loop. Dr. John vans drove Sherry Gluchowski’s kidney through Milner, a transplant surgeon at Loyola, said he then stop-and-go traffic on Interstate 405 to the Los selected Mr. Terry to receive the kidney because he Angeles airport. Cynthia Goff, an operations was the best immunological match on the hospital’s supervisor for the courier company who had wait list. volunteered to accompany the kidney to Chicago, When Dr. Milner called with the news in early rolled the box into the terminal strapped atop her December, Mr. Terry was floored at his remarkable carry-on with a bungee cord. A pit bull, waiting to be good fortune. Having felt unfairly condemned when placed in its travel kennel, strolled by and sniffed. he was first placed on dialysis, he now wondered After security agents checked the box with a what he had done to deserve a gift that 90,000 desktop scanner, Ms. Goff rolled the kidney down others needed just as much. the concourse, past a currency exchange and a 278 VEALE AND HIL

As it sank in that his would be the last of 30 to continue?” he asked Dr. Milner. “I don’t want to interconnected transplants, Mr. Terry began to feel be the reason to stop anything.” guilty that he would be ending the chain. “Is it going “No, no, no,” the doctor reassured him. “This chain ends, but another one begins.”

SUMMARY Since organizing its first swap in 2008, the cross match accuracy has improved from 43% National Kidney Registry had facilitated 389 to 94% as a result of improvements in the HLA kidney transplants by the end of 2011 across typing process for donor antigens and enhanced 45 U.S. transplant centers. Rapid innovations, mechanisms to list unacceptable HLA antigens advanced computer technologies, and an for sensitized patients. By the end of 2011, the evolving understanding of the processes NKR had transplanted 66% of the patients at participating transplant centers and enrolled since 2008. The 2011 wait time (from histocompatibility laboratories are among the enrollment to transplant) for the 175 patients factors driving the success of the NKR. Virtual transplanted that year averaged 5 months.

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