National Kidney Registry

National Kidney Registry

Type	Nonprofit
Industry	Healthcare
Founded	July 12, 2007
Headquarters	Babylon, New York, U.S.
Area served	U.S.
Website	kidneyregistry.org

The National Kidney Registry (NKR) is the largest paired exchange program in the United States and facilitates over 360 paired exchange transplants annually.^[1][2] The NKR was founded by the Hil family in 2007 after their youngest daughter lost her kidney function at age ten. Both parents were ruled out from donating to their daughter because they were biologically incompatible. Finally, after unsuccessful attempts to find a compatible donor through all of the kidney paired exchange programs in the United States, a compatible donor was found. After their transplant ordeal, the Hil family founded the National Kidney Registry to eliminate the problem of incompatible donors by building a national kidney paired donation program (KPD).^[3] Mr. Hil was the first KPD leader to donate one of his kidneys to start a chain. His kidney donation 2015 initiated a swap that facilitated 8 transplants. The success of the NKR has generated significant media coverage including a front page story in the New York Times ^[4] and nationally televised interviews by Katie Couric with CBS Evening News,^[5] Diane Sawyer from ABC News,^[6] and Byron Pitts at Nightline.^[7]

The Problem

More than one-third of potential living kidney donors who want to donate their kidney to a friend or family member cannot because of blood type or antibody incompatibility.^[8] Historically, these donors would be turned away and the patient would lose the opportunity to receive a life-saving transplant. KPD overcomes donor-recipient incompatibility by swapping kidneys between multiple donor-recipient pairs.

History

The NKR was founded in 2007 and organized its first swap on Valentine’s Day in 2008 at Cornell Medical Center in New York City.^[9] This first swap was a 3-deep chain that ended with a bridge donor who donated two months later, extending the chain to 5-deep.^[10] This chain was broken after the bridge donor reneged following many failed cross matches that required the donor to repeatedly go to the hospital for blood draws. The NKR’s second swap started with the shipment of a kidney from Cornell to UCLA. This was the first time a living donor kidney was shipped on a commercial airplane. This second chain crossed the country three times, facilitating eight total transplants at UCLA, Cornell, Stanford and CPMC. Ultimately, this chain was broken when the bridge donor reneged.^[11] Based on these early experiences, many safe guards were implemented to reduce the risk of broken chains, which dropped the frequency of broken chains from 33% in 2008 to 2% in 2015.^[2]

In 2012, the NKR broke the world record for the largest kidney swap by organizing a 30-deep chain involving 60 donors and recipients. This chain was started by Rick Ruzzamenti a 44-year-old from Riverside, California. The swap took four months to complete and involved 17 different transplant centers across 11 states.^[12] Three years later, on March 26, the next record breaking chain was set into motion by Kathy Hart, a 48-year-old attorney from Minneapolis. This swap took two months to complete and involved 26 different transplant centers.^[13]

Key Innovations

The rapid growth of KPD transplants in the United States has been driven by the following key NKR innovations.

• Shipped Kidneys - The NKR was the first KPD program to utilize commercial airlines to ship kidneys.^[11] This allows kidney donors to undergo surgery near their home, eliminating the need to travel to a distant city to donate. This innovation has evolved to include the use of charter jets and turbo-prop aircraft, on board couriers for connecting flights, charter flights combined with direct commercial moves, red-eye flights from West to East, and helicopter transport for shorter distances.
• HLA coding standardization - In the startup period, the NKR experienced virtual cross match failure rates in excess of 50% because HLA coding schemes were not sufficiently standardized in the United States. The NKR implemented a standardized HLA coding scheme and forced the identification of more antigen and antibody data such as DP, Bw, Cw, DQ and DQA.^[14] This refinement and expansion of HLA data increased the virtual cross match accuracy from less than 50% to greater than 95% allowing more patients to get transplanted in a shorter period of time.^[15]
• Finance & contracting - In late 2009, a 3-deep cluster being organized by the NKR fell apart the day before the swap was scheduled to commence because the hospitals in the swap could not agree on how to pay each other for the donor surgeries. Not only did this swap fall apart, but the last minute cancellation was the catalyst for a broken chain as the bridge donor for this cluster eventually withdrew. In response to this and prior financial challenges, the NKR assembled a team of finance experts from member centers and developed a financial model that would eliminate these challenges. Once the financial model was agreed upon by all member centers, the NKR created a universal “center to center agreement” that would allow any member center to ship a kidney to, or accept a kidney from, another member center.^[16]
• GPS tracking - In 2010, the NKR implemented the first GPS tracking systems used for shipping organs in the United States.^[17] After several near misses including a case where a kidney was off-loaded from an “overweight” midnight red-eye flight out of LAX, the NKR made GPS tracking mandatory for all kidney shipments. In this case the kidney sat in the baggage storage area for approximately two hours before it was discovered by an airline employee. An emergency private jet was ordered and later departed Los Angeles at 4:00 AM. The kidney arrived in Philadelphia on time and was successfully transplanted. By 2015, the NKR was the largest user of GPS tracking systems in the United States for organ shipments.
• SMELAC - KPD matching is characterized as an NP-Hard problem in computational complexity theory.^[18] There are several ways to approach the KPD matching problem. The NKR uses an exhaustive search algorithm with expert system selection logic based on the NKR Medical Board's match offer selection policy.^[19] The exhaustive search algorithm would require supercomputer resources if not for the NKR's use of donor preselect screening, which was patterned from brokerage industry limit orders and eliminates matches that will ultimately be declined. The initial NKR matching algorithm included only chain (Domino & NEAD) based matching for 2 deep chains. By 2009 the matching engine was extended to 3 deep chains, then 6 deep chains, then 12 deep chains. In 2010, stand alone loop matching was implemented along with an upgrade that accommodated 20 deep chains. In 2011, a major upgrade of the matching engine enabled Simultaneous Mutually Exclusive Loops and Chain (SMELAC) matching.^[20] The SMELAC algorithm allowed the NKR to determine if the utilization of a chain, a loop or both would be the best approach for any given match run.
• Repairing real-time swap failures - A real-time swap failure occurs when a swap falls apart after one or more donor surgeries have begun, leaving a patient, whose donor has already donated, without a kidney. Real-time swap failures can occur when a donor surgery must be aborted due to previously undetected donor medical conditions and when a recipient reacts badly to the surgery after the surgery has started. The NKR's historical statistics indicate that a real time-swap failure occurs once every 200 - 300 transplants.^[21] Out of the 7 real-time swap failures that the NKR experienced by the end of 2015, all patients that were initially left without a kidney when the swap failed, received a kidney within 1 – 6 months. Chain end donors and non-directed donors are the only way to recover from a real-time swap failure. The NKR has been able to quickly repair swap failures because of the large number of chains it starts each year including 83 chains in 2015.^[2]
• Exploratory cross matching - Exploratory cross matching for KPD was pioneered by Dr Adam Bingaman at the Methodist Specialty & Transplant, Hospital to test for HLA compatibility in advance of initiating a swap.^[22] In 2013, the NKR adopted this approach in a multi-center environment to test donor, patient compatibility before a match is offered.^[23] Although NKR's adoption of exploratory cross matching helped a few highly sensitized patients get transplanted and reduced the rate of swap failures due to unacceptable cross match results, it was not until the implementation of donor blood cryo-preservation in 2015 that exploratory cross matching yielded substantial results.
• Cryo-preserved donor blood - Human blood can be cryo-preserved and stored indefinitely in liquid nitrogen freezers at a temperature of -196 °C to facilitate rapid cross matching without requiring fresh blood from donors.^[24] In 2015, the NKR created a national lab service, so cryo-preserved donor blood could be stored for donors across NKR's 70+ member centers. The implementation of the cryo-preservation service allowed NKR centers to dramatically reduce the time to complete a cross match from 1–2 weeks to 1–2 days, facilitating more transplants for highly sensitized patients and reducing swap failures caused by unacceptable cross matches. Donor blood cryo-preservation also reduces the number of times a donor needs to have blood drawn for cross matching, making paired exchange more convenient for donors.^[23]
• Advanced Donation Program - The Advanced Donation Program (ADP) is a paired exchange separated in time. This program allows living donors to donate their kidney before their Intended Recipient receives a kidney. Some ADP donors have donated only a few weeks before their Intended Recipients received a kidney. Some ADP donors are donating 10–20 years before their Intended Recipient expects to need a transplant, and some ADP donors are donating in the hope that their Intended Recipient will never need a transplant. Garet Hil, Founder of the NKR, donated his kidney through the ADP program in 2015. Most long term ADP cases involve older donors who want to donate on behalf of their intended recipient before they become too old to donate.^[25]

Academic Publications

The work done by the NKR has inspired numerous academic publications relating to the field of KPD. Many of these publications are authored by researchers from NKR Member Centers who have helped advance the field of KPD. Below are a list of some of these publications.^[26]

1. ABO-Incompatible Kidney Transplants: Twice as Expensive, Half as Good
2. The Incorporation of an Advanced Donation Program into Kidney Paired Exchange
3. Equipoise: Ethical, Scientific, and Clinical Trial Design Considerations for Compatible Pair Participation in Kidney Exchange Programs
4. Optimizing HLA matching in a highly sensitized pediatric patient using ABO-incompatible and paired exchange kidney transplantation
5. Demographic and Clinical Characteristics of 207 Non-Directed Donors Participating in Paired Exchange through the National Kidney Registry
6. Outcomes of shipped live donor kidney transplants compared with traditional living donor kidney transplants
7. A Systematic Review of Kidney Paired Donation: Applying Lessons From Historic and Contemporary Case Studies to Improve the US Model
8. Center-Defined Unacceptable HLA Antigens Facilitate Transplants for Sensitized Patients in a Multi-Center Kidney Exchange Program
9. Kidney Transplant Chains Amplify Benefit of Nondirected Donors
10. Chain Transplantation: Initial Experience of a Large Multicenter Program
11. Better HLA Match = Lower Patient Mortality
12. The National Kidney Registry: 175 Transplants in One Year
13. Living donor kidney paired donation transplantation: experience as a founding member center of the National Kidney Registry
14. Boosting Renal Transplantation with Kidney Paired Donation
15. Kidney Paired Donation: Something Special
16. Managing Finances of Shipping Living Donor Kidneys
17. National Kidney Registry: 213 Transplants in Three Years
18. The National Kidney Registry: Transplant Chains - Beyond Paired Kidney Donation
19. Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel Concept
20. Does flow cytometry crossmatch predict renal allograft outcome in patients with a negative antiglobulin crossmatch?

References

1. Transplant:Donor Relation by Transplant Center (Report). Organ Procurement and Transplantation Network. Retrieved 6 Apr 2016.
2. Paired Exchange Results Quarterly Report (Report). National Kidney Registry. 2015.
3. "Message from the Founder". www.kidneyregistry.org. National Kidney Registry. Retrieved 6 Apr 2016.
4. Sack, Kevin (18 Feb 2012). "60 Lives, 30 Kidneys, All Linked". New York Times.
5. Couric, Katie (10 Nov 2010). "Kidney Chains Link Strangers". CBS Evening News.
6. Sawyer, Diane (20 Feb 2012). "Kidney Donation Leads to Unexpected Kindness". ABC News.
7. Pitts; Louszko; Cappetta; Effron; Valiente (15 Apr 2015). "Changing Lives Through Donating Kidneys to Strangers". ABC News Nightline.
8. Segev; Gentry; Warren; Reeb; Montgomery (20 Apr 2005). "Kidney Paired Donation and Optimizing the Use of Live Donor Organs". 293 (15). Original Contribution: 1883–1890.
9. "First Valentine's Day Donor Chain" (Press release). National Kidney Registry. 20 Feb 2008.
10. "Acts of Kindness Between Strangers". NBC New York Nightly. Retrieved 7 Apr 2016.
11. Butt; Gritsch; Schulam; Danovitch; Wilkinson; Del Pizzo; Kapur; Serur; Katznelson; Busque; Melcher; McGuire; Charlton; Hil; Veale (29 Apr 2009). "Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel Concept". 9 (9). American Journal of Transplantation: 2180–2185.
12. "Largest Kidney Donor Chain: National Kidney Registry sets world record". www.worldrecordacademy.com. World Record Academy. 21 Feb 2012.
13. Pitts; Louszko; Cappetta; Effron; Valiente (14 Apr 2015). "Donating a Kidney to a Complete Stranger in Order to Save a Loved One". ABC News.
14. Baxter-Lowe; Cecka; Kamoun; Sinacore; Melcher (26 Feb 2016). "Center-Defined Unacceptable HLA Antigens Facilitate Transplants for Sensitized Patients in a Multi-Center Kidney Exchange Program". XX. American Journal of Transplantation: 1–7.
15. Veale; Hil. "National Kidney Registry: 213 Transplants in 3 Years". Clinical Transplants 2010: 333–344.
16. Mast; Vaughan; Busque; Veale; Roberts; Straub; Flores; Canari; Levy; Tietjen; Hil; Melcher (8 June 2011). "Managing Finances of Shipping Living Donor Kidneys for Donor Exchanges". American Journal of Transplantation.
17. "NKR Introduces GPS Tracking Technology" (Press release). National Kidney Registry. 16 Aug 2010.
18. Timmer (6 Jan 2015). "The math of organ donation:Kidneys are an NP-Hard problem". Ars Technica.
19. "Medical Board Policies". www.kidneyregistry.org. National Kidney Registry. Retrieved 10 Apr 2016.
20. Veale; Hil (9 Apr 2012). "The National Kidney Registry:175 Transplants in One Year". Clinical Transplants 2011.
21. "Where Are We Going with Kidney Paired Donation? A Nationally-run Private Program Works Best". American Society of Transplantation.
22. Bingaman; Wright Jr.; Kapturczak; Shen; Vick; Murphey (1 Mar 2012). "Single-Center Kidney Paired Donation: The Methodist San Antonio Experience". 12. American Journal of Transplantation: 2125–2132.
23. "National Kidney Registry Initiates Donor Blood Cryo-Preservation" (Press release). National Kidney Registry. 2 Dec 2014.
24. Berz; McCormack; Winer; Colvin; Quesenberry (12 Nov 2007). "Cryopreservation of Hematopoietic Stem Cells" (PDF). 82 (6). National Institute of Health: 1–16. PMC 2075525.
25. Flechner; Leeser; Pelletier; Morgievich; Miller; Thompson; McGuire; Sinacore; Hil (31 Mar 2015). "The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry". XX. American Journal of Transplantation: 1–6.
26. "Academic Publications". www.kidneyregistry.org. National Kidney Registry. Retrieved 7 Apr 2016.