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A SIMPLE LAW OF ECONOMICS: when demand outweighs supply, the price of a commodity rises. But what if the commodity is a human kidney, which by law cannot be sold? Who should receive first priority? The person who has waited the longest or the one who is the sickest? What about the person who is the best biologic match for the kidney, regardless of wait time?
     The answers are far from black and white. Of the more than 65,000 people in the United States on the waiting list for a kidney transplant, approximately 4,000 will die this year because they were unable to receive an organ in time. Current national policy in matching kidneys to recipients tends to favor patients who have spent the longest time on the wait list.
     Researchers at Emory have long worked toward a better method of kidney allocation, and they have developed a new system that gives hope to one of the most disadvantaged groups on the waiting list, so-called sensitized patients. Sensitized patients are those who have developed antibodies against human leukocyte antigens (HLAs), which play an important role in the body’s immune response to foreign tissue. Such antibodies usually result from a prior pregnancy, blood transfusion, or previous transplant. The Emory Algorithm, as the new method for kidney allocation is known, may even change the way kidneys from deceased donors are allocated in this country.
     The United Network for Organ Sharing (UNOS) coordinates the nation’s transplant system through a point system based primarily on wait time, sensitization, and HLA matching. When a kidney becomes available anywhere in the country, the UNOS computer creates a list that prioritizes recipients based on these criteria. When a “perfect match” occurs, the kidney is offered to the person at the top of the national list. If there are no perfect matches on the national list, the kidney is next made available to transplant centers in the region from which it came, and in turn each of those centers runs a match list. While many transplant centers replicate the UNOS allocation policy, some regions have received permission to deviate from the standard.
     The Emory Algorithm takes a different approach, while still following these guidelines. For the sensitized patients (who make up approximately 50% of Georgia’s wait list), the Emory Algorithm predicts which patients on the list will be compatible with any given donor. The algorithm’s developers—immunologists Robert Bray and Howard Gebel and transplant surgeons Christian Larsen and Thomas Pearson—say the method may help level the playing field for sensitized patients, who rarely make it to surgery because a compatible match is seldom identified. In the United States, although sensitized patients represent one-third of the wait list, on average they receive approximately 15% of deceased-donor kidney transplants each year. Using the Emory Algorithm, its developers found they could raise the rate of transplants to 25% in sensitized patients. The results of their five-year study appeared in the October 2006 issue of the American Journal of Transplantation.
  Better than a best guess
The Emory Algorithm uses a relatively new technology of single-antigen bead assays, which give a more specific analysis of HLA antibodies. With the degree of specificity the assays provide—identifying a single antibody versus general groups of antibodies—immunologists can inform transplant surgeons with a high degree of confidence whether a kidney from a deceased donor is a compatible match with a given recipient. No more making a “best guess,” says Bray.
     “Each of us has a constellation of HLAs, with six major ones related to kidney transplantation,” Bray says. “With the older technique of cross-matching HLA cells with the blood of a potential recipient, we couldn’t always identify which HLAs the antibodies were targeting. False readings could occur.”
     Everyone has an A, B, and DR antigen from each parent, making up the six antigens important to transplantation. Within each antigen group are numerous specific antigens, sometimes dozens. There are nearly 50 B antigens alone. Studies have shown the more A, B, and DR antigens a donor and recipient share, the better the survival rate of the transplanted kidney.
     Emory’s Algorithm incorporates a filtering process into the match, effectively removing patients with antibodies against the donor because antibodies to HLAs are what really matter, Pearson says. A poorly HLA-matched kidney without antibodies is better than a well-matched kidney with antibodies. And the single-antigen bead assay test is key to determining which HLA antibodies are present.
     A decade ago, Bray and Gebel helped One Lambda, an HLA diagnostic company in California, develop and test its single-antigen bead assays. Each bead is coated with a single HLA antigen produced by recombinant DNA technology. Different HLA molecules are bound onto different antigen bead assays. The beads are mixed with the recipient’s blood and then placed in a flow cytometer, a machine the size of a window air-conditioner. Inside the flow cytometer, a laser reads what antibodies, if any, are attached to the HLA molecules on the beads. A computer then collects and organizes the results. The process takes less than four hours, from start to finish.
     While some transplant centers use these same single assay tests to identify HLA antibodies, they fail to incorporate the data into their match run. Thanks to the Emory Algorithm, sensitized patients have an increased chance of receiving a transplant.
     “Kidney transplantation is the optimal treatment for end-stage renal disease, and being able to offer transplantation to this population is a significant advance,” says Pearson.
     Pearson says the Emory Algorithm showcases how technology can be used to define nature’s barriers to improve transplantation—essentially helping you work better with what you’ve been given.
     Other methods that break down barriers before transplantation, such as plasmapheresis—a blood-filtering process that removes a recipient’s antibodies in preparation for a transplant from a living donor—are costly and carry a high risk of complications.
     Within the Emory study, the survival rate of a kidney transplant in sensitized patients after five years was almost identical to that of unsensitized recipients—66% versus 70%, respectively. “There is a perception in the literature that patients who are highly sensitized have poor outcomes,” says Gebel, “but that’s not our experience.”
  Reviewing the national policy
Based on results of the Emory study, a UNOS committee is looking at the algorithm as UNOS reevaluates its kidney allocation system. The committee is expected to make recommendations this year, according to Mark Stegall, a transplant surgeon at the Mayo Clinic and the committee chair. Pearson also sits on the committee.
     “I hope the algorithm process will become national policy as part of an overall kidney allocation policy,” Stegall says. “Eighty percent of transplant programs are using the single-antigen bead technology, but relatively few are using that data to allocate kidneys to sensitized patients. Emory has been a thought leader in this for many years. They’ve provided a great resource to the transplant community.”
     Still Stegall is not ready to commit to a system based only on organ compatibility as determined by antibodies. “Kidneys are a scare resource,” he says. “We have to put sensitization in perspective. There is always an unsensitized patient out there.”
     No allocation system for kidney transplants can be 100% fair to every patient, Pearson says, although the Emory Algorithm helps equalize the allocation scheme. With this system, everyone on the waiting list would be considered for an available kidney, but only the best match would receive it.
     “There is no ‘right’ answer and no ‘fair’ as long as the number of patients with kidney failure far exceeds the number of kidneys available for transplant,” Pearson says. “We have to balance priorities to try and help as many people as possible.”


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