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Kidney Chains Amplify the Benefit of Living Donations

Chain Reactions: Amplifying the Impact of Living Donations Through Kidney Chains

"You think you have an insoluble problem, and then human beings come to the aid of each other in a great way to solve that problem."

—Titte R. Srinivas, M.D., Medical Director of Kidney and Pancreas Transplant Programs at MUSC, describing the kidney chain

Every year, 100,000 patients are placed on the waiting list for kidney transplants. Of those, only slightly over 20,000 receive kidneys, 16,000 or so from deceased donors and 6,500 from living donors. That means that four out of five patients in need of a kidney go without one, many of whom must in the meantime rely on dialysis. Extended times on dialysis are associated with worse outcomes after transplant and place a huge economic burden on the health care system.

This cruel math has meant that many die while awaiting a kidney. And, despite all efforts, this resource problem—a demand that far outstrips supply—has long remained a riddle that could not be solved.

It took a man for whom those numbers became very personal, a man whose daughter’s life hung in the balance, to find a way to fuse creative mathematics/economics and the power of human generosity into a solution for this seemingly hopeless dilemma. The answer to the riddle would be the kidney chain.

There Must Be A Better Way

No nightmare could be worse for parents than not being able to give their child something he or she desperately needs. That was the nightmare faced by Garet Hil and his wife Jan when their ten-year-old daughter’s kidneys failed. Family member after family member stepped up to donate, only to find out that they were not a suitable match. An anonymous donor was also incompatible. Attempts to join paired kidney exchange networks, scattered throughout the United States, proved frustrating. Finally, after screening a dozen donors, a compatible match was found and Garet Hil’s daughter underwent a kidney transplant. She and her donor are both doing well today.

But why did it have to be so difficult?

An entrepreneur in digital publications, Hil wondered whether computer programs could be used to facilitate the matching of compatible donors and recipients. He founded the National Kidney Registry (NKR), which enrolls living donors and patients in need of a transplant and uses a sophisticated algorithm to find matches between them. More than 70 institutions, including MUSC, participate in the registry.  

The algorithm, developed in cooperation with and optimized by Alvin E. Roth of Harvard University and Lloyd S. Shapley of the University of California at Los Angeles, who won the 2012 Nobel Prize in Economics for their work, seeks to improve the allocation of fixed resources by optimizing the match between different agents, whether that be matching student applicants with schools or organ donors with patients needing a transplant.

Making a Good Match

What makes a good match between kidney donor and recipient? First, their blood types must be compatible. Second, they must be immunologically compatible, ie, the recipient must not have preformed antibodies against the donor’s human leukocyte antigens (HLA). Because a child inherits one HLA haplotype (comprising an A, B, and DR protein) from each parent, siblings have only a 25% chance of having an identical HLA haplotype, meaning that many family members will not prove a good match for a child in need of a transplant . Antibodies to HLA can build up in the blood due to previous transplant, blood transfusions, or pregnancy. Garet Hil could not donate a kidney to his daughter because she had built up antibodies to his antigens after receiving a blood transfusion from him.

According to Titte R. Srinivas, M.D., Medical Director of the Kidney and Pancreas Transplant Programs at MUSC, “The beauty of the NKR system is you are not restricted to your designated donor. Your donor can give to the NKR list and it expands your options.” Sara Parker, R.N., MUSC’s NKR coordinator, echoes this point: “A patient with a living donor is not bound to that one donor—that donor is a ticket into an exchange where there is greater genetic diversity and a greater chance of a good match.” In short, having a living donor, albeit an incompatible one, gains one right of entry into the NKR, where the right kidney might await.

What is a Kidney Chain?

The sophisticated algorithm used by the NKR helps identify donors and recipients who would likely be good matches, though they may live in distant parts of the United States. But, to realize the potential of these identified matches, a spark of human generosity is required.

The chain of kidney transplants is set off with an altruistic donation. A non-directed donor offers up a kidney without designating a recipient.  Using the algorithm, that kidney can be matched with an appropriate recipient in the NKR registry, who has a willing living donor who has proven to be incompatible. The incompatible donor of the first recipient in turn “pays it forward” by donating his or her kidney to a recipient that is a good match for that kidney (Figure), and the process continues on until a kidney comes back to the institution where the originating non-directed donation occurred or is given to a patient enrolled in the Children and High Panel-Reactive Antibody (PRA) Program (CHIP). Patients in need of a kidney transplant undergo a PRA test, which determines the proportion of the population with which they are likely to be immunologically incompatible (score, 0%-99%). Patients with a high PRA, known as sensitized patients, are likely to reject organs from most donors and so are very hard to match, meaning they have to wait longer on the list for a kidney. According to Joe Sinacore of the NKR, It is for this reason that “we try to end a chain with the most disadvantaged patients.”  Receiving the final “surplus” kidney in a kidney chain, CHIP participants are not expected to identify a living donor of their own to begin another cluster. As an NKR-affiliated institution, MUSC is granted 50 CHIP slots and is currently awaiting a kidney for someone in that program as “repayment” for the non-directed donation of April 3.

Garet Hil, who almost lost his own child when her kidneys failed, is overjoyed that MUSC has joined the NKR because that means more people with incompatible donors will be transplanted, but he is particularly excited by MUSC’s CHIP participation: “The additional focus on getting children transplanted at MUSC is especially exciting and something that everyone at MUSC should be extremely proud of.”

The number of transplants that occur as part of a kidney chain can range from one to as many as thirty (a chain with thirty transplants was recently featured in the New York Times1). Most chains are completed within one to two months, though some can extend further. Although the likelihood of finding a good genetic match grows with the size of the chain, so too does the chance that it could break down for logistical reasons or because someone backs out. However, a recent study shows that the number of broken chains is decreasing as the program grows.2 The program is also becoming more adept at pausing a chain if a problem occurs and then restarting it when the problem is resolved. If, for example, three transplants have occurred in a chain but the incompatible living donor of the third recipient is ill or for some other reason cannot make the donation needed to carry the chain forward at the prescribed time, the chain can be paused. The program will work to restart the chain as soon as possible, encouraging the donor to act as a bridge donor, ie, to initiate a new set of transplants by donating his or her kidney to a compatible stranger. Although such donors could lose motivation because their intended recipient has already received a kidney, most go forward with the donation. Each set of transplants before a pause is known as a cluster; very long chains such as that covered by the New York Times typically consist of several clusters, linked together by willing bridge donors.

The NKR also contracts with a private courier to help coordinate the logistics of shipping the donated kidney to the recipient.  Kidneys travel unattended on commercial flights with a GPS tracker that alerts coordinators at both the donor and recipient hospitals as to its whereabouts every thirty minutes. A backup commercial flight is also identified in case anything goes wrong (ie, a flight is delayed). As a last resort (due to cost), a private flight for the kidney can be arranged. Although efforts are made to identify a kidney as close as possible to a would-be recipient, chains involving one or more transcontinental flights have resulted in excellent outcomes.3

How Do Patients Benefit from Kidney Chains?

By helping solve the problem of incompatibility, the kidney chain makes more living donations possible. Kenneth D. Chavin, M.D., PhD, Professor of Surgery, Microbiology, and Immunology and Surgical Program Director for the Living Donor Program at MUSC, estimates that participation in kidney chains could increase the number of living donor kidney transplants at MUSC from 30-35 to 50-60 per year: “This is us trying to find another opportunity to get more kidneys for our patients on the wait list to have successful outcomes of transplants—availing ourselves of all technology to accomplish that.”

Previously, virtually the only recourse for a would-be recipient whose living donor had proven incompatible would be to submit to toxic immunosuppressive therapy (ie, desensitization) in the hopes of preventing his or her antibodies from attacking the donated organ.  The higher likelihood of finding a compatible kidney through kidney chains made possible by the NKR should reduce the need for desensitization.  According to Prabhakar Baliga, M.D., Chief of the Division of Transplant Surgery at MUSC and the Surgical Program Director for the Kidney Program, “one-year data on kidney graft survival shows a 10-point improved survival for living donor exchange vs desensitization…without the need to hit patients with such powerful immunosuppressive medications.”

A living donation made possible by a kidney chain also offers the recipient an organ that is much healthier and likely to last much longer than that from a deceased donor because it has not gone through the cascade of death. A kidney from a living donation begins functioning immediately, whereas the kidney from a deceased donor has “gone to sleep” and may take some time to begin functioning again (delayed graft function) and may never function as well as a living kidney.

Patients can also rest assured that a kidney obtained through a kidney chain has undergone the same rigorous screening process as a kidney that originated at MUSC. In addition, physicians at MUSC are allowed to set requirements for the quality of organ that they are willing to accept. For example, MUSC will not accept an organ from an older adult (>45 years) for transplant in a child because they want the graft to last as long as possible. It has also turned down kidneys from donors with conditions such as atherosclerosis because such a kidney likely has already sustained some damage that would compromise the success of the graft. It is not penalized for such high standards; it will continue to be offered kidneys on a priority basis until an acceptable match is found to “repay” the non-directed donation.

Amplifying a Good Deed

For the voluntary donor, the kidney chain offers an opportunity to magnify the impact of their good deed. Instead of helping one, the donor is instrumental in helping many. Michael Denson, whose April 3 donation kick started MUSC’s first kidney chain, became interested in participating in a kidney chain because, in his words, “I wanted to see as much bang for my buck as possible from my donated kidney.” Instead of helping one child, as he had originally intended when he decided to become a living donor, Denson initiated a chain that resulted in transplants for seven people. Because it started the chain, MUSC will receive a kidney for a child or adult enrolled in the CHIP program. In addition, the seven people who received kidneys have been removed from the deceased donor waiting list, meaning that seven others can move up on that list and receive a donation from a deceased donor sooner. The selfless act of one donor, amplified by the matching capacities of the NKR’s algorithm, has helped save the lives of at least eight people and contributed to the saving of seven more.  Talk about the loaves and the fishes.

Denson remains surprised that only about 1,000 of the nation’s 70,000 would-be kidney recipients are enrolled in the NKR. He wonders whether more people would participate if they knew that
“the National Kidney Registry and the paired kidney exchange offer a better opportunity for a better match over a shorter period of time while avoiding dialysis. That is something that has to be desirable to the patient and to any loved ones willing to be a living donor.” He would certainly get no argument from Garet Hil.

For more information on the availability of kidney chains at MUSC, contact Sarah Parker, R.N., NKR coordinator, at burbages@musc.edu

References

1 Sack K. 60 lives, 30 kidneys, all linked. New York Times. February 18, 2012. Available at http://www.nytimes.com/2012/02/19/health/lives-forever-linked-through-kidney-transplant-chain-124.html.

2 Melcher ML, Veale JL, Javaid B, et al. Kidney  transplant  chains  amplify  benefit of nondirected donors.JAMA Surg 2013;148(2):165-169.

3 Butt FK, Gritsch HA, Schulam P, et al. Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel Concept. Am J Transplant 2009;9(9):2180-2185

This article originally appeared in the August 2013 issue of Progressnotes.

KEY POINTS

  • The National Kidney Registry (NKR), which MUSC joined in late 2011, matches living donors with compatible recipients using a sophisticated algorithm, making chains of kidney transplants possible.
  • Patients with living donors who prove to be incompatible need not give up on the idea of living donation; because they have identified a willing living donor, albeit an incompatible one, they can be entered into the NKR for inclusion in a kidney chain.
  • A kidney chain starts with the donation of a kidney by a non-directed donor (ie, a donor who does not designate the recipient of his or her donated organ). That kidney is then transplanted into a compatible patient listed in the NKR; the incompatible donor of the first recipient donates his or her kidney to a compatible stranger in the NKR, and the process continues until a kidney returns to the first institution or until a bridge donor starts a new cluster.
  • MUSC initiated its first kidney chain on April 3 with a non-directed donation that to date has resulted in seven transplants and will result in a kidney coming to a hard-to-match patient (likely a child) at MUSC.
  • The kidney chain offers many benefits to those in need of a transplant: on average, it shortens the time spent waiting for a kidney; it provides a very good-quality, living kidney that is very compatible to the recipient, making it much less likely that it will be rejected; it thereby reduces the need for and avoids the adverse effects of desensitization; and it helps those who are hard to match, such as those with a high Panel-Reactive Antibody score, be transplanted. Most important of all, the outcomes of paired kidney donation are superior to those achieved by desensitization.