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In the anguishing wait for a new kidney, tens of thousands of patients on waiting lists may never find a match because their immune systems will reject almost any transplanted organ. Now, in a large national study that experts are calling revolutionary, researchers have found a way to get them the desperately needed procedure.
In the new study, published in The New England Journal of Medicine, doctors successfully altered patients’ immune systems to allow them to accept kidneys from incompatible donors. Significantly, more of those patients were still alive after 8 years than patients who had remained on waiting lists or received a kidney transplanted from a deceased donor.
The method, known as desensitisation, “has the potential to save many lives,” said Dr Jeffery Berns, a kidney specialist at the University of Pennsylvania’s Perelman School of Medicine and the president of the National Kidney Foundation.
It could slash the wait times for thousands of people and for some, like Clint Smith, a 56-year-old lawyer in New Orleans, mean the difference between receiving a transplant and spending the rest of their lives on dialysis. The procedure, Smith said, “changed my life.”
Researchers estimate about half of the 100,000 people in the United States on waiting lists for a kidney transplant have antibodies that will attack a transplanted organ, and about 20% are so sensitive that finding a compatible organ is all but impossible.
In addition, said Dr Dorry Segev, the lead author of the study and a transplant surgeon
at the Johns Hopkins University School of Medicine, an unknown number of people with kidney failure simply give up on the waiting lists after learning that their bodies would reject just about any organ. Instead, they resign themselves to dialysis, a difficult and draining procedure that can pretty much take over a person’s life.
Desensitisation involves first filtering the antibodies out of a patient’s blood. The patient is then given an infusion of other antibodies to provide some protection while the immune system regenerates its own antibodies.
For some reason — exactly why is not known — the person’s regenerated antibodies are less likely to attack the new organ, Segev said. But if the person’s regenerated natural antibodies are still a concern, the patient is treated with drugs that destroy any white blood cells that might make antibodies that would attack the new kidney.
The process is expensive, costing $30,000, and uses drugs not approved for this purpose. The transplant costs about $100,000. But kidney specialists argue that desensitisation is cheaper in the long run than dialysis, which costs $70,000 a year for life.
Although, by far the biggest use of desensitisation would be for kidney transplants, the process might be suitable for living-donor transplants of livers and lungs, researchers said.
The liver is less sensitive to antibodies so there is less need for desensitisation, “but it’s certainly possible if there are known incompatibilities,” Segev said. With lungs, he said, desensitisation “is theoretically possible,” although he said he was not aware of anyone doing it yet.
In the new study, 1,025 patients at 22 medical centres who had an incompatible donor were compared to an equal number of patients who remained on waiting lists for an organ or who had an organ from a deceased but compatible donor.
After eight years, 76.5% of those who received an incompatible kidney were still alive, compared with 62.9% who remained on the waiting list or received a deceased-donor kidney and 43.9% who remained on the waiting list but never got a transplant.
The desensitisation procedure takes time — for some patients as long as two weeks — and is performed before the transplant operation, so patients must have a living donor. It is not known how many have someone willing to donate a kidney, but doctors say they often see situations in which a relative or even a friend is willing to donate but is incompatible.
“Often patients are told that their living donor is incompatible, so they are stuck on waiting lists” for a deceased donor, Segev said.
In recent years, an option called a kidney exchange has helped some in this situation. Patients who have incompatible living donors can swap donors with someone whose donor may be compatible with them. Often, there are chains of patient-donor pairs leading to a compatible organ swap.
That process can be successful, said Krista L Lentine, the medical director of the living donation programme at the St Louis Centre for Transplantation, but patients often still cannot find a compatible organ because they have antibodies that would reject almost every kidney. In those cases, “desensitisation may be the only realistic option for receiving a transplant,” said Lentine, who was not involved with the study.
Emotional bond
Dr Jeffrey Campsen, a transplant surgeon at the University of Utah Health Sciences Centre who also was not a study investigator, said his group focused on exchanges and had been fairly successful. But he also comes across patients whose donors do not want to participate.
“There is a hurdle if the donor and patient have an emotional bond,” he said. The new data showing the success of desensitisation “lets people get behind it,” Campsen said, adding, “I do think it is something we would consider.”
Smith, the New Orleans patient who went through desensitisation, had progressive kidney disease that slowly scarred his kidneys until, in 2004, they stopped functioning. His sister-in-law, Allison Sutton, donated a kidney to him, and he had a transplant, but after 6 1/2 years, it failed. He went on dialysis, spending four days a week hooked up to dialysis machines for hours. It was keeping him alive, he told his friends, but it was not a life.
Then a nurse suggested that he ask Johns Hopkins about its desensitisation study. “I was like, whatever I could do,” he said. He discovered that he qualified for the study. But he needed a donor.
One day, his wife was talking on the phone to a college friend, Angela Watkins, who lives in Augusta, Georgia, and mentioned that Smith was praying for a donor. Watkins’ husband, David Watkins, a judge in state court, had been friends with Smith in college and the two wives, also college friends, had kept in touch over the years. Watkins told her husband about the conversation, and they asked themselves if they should offer to donate.
“We talked and researched and prayed,” David Watkins said. Finally, he said, they came to a conclusion. “We have a moral obligation to at least see if we would qualify.” And he thought that he should be the one to go first. If he did not qualify, his wife could be tested.
That was four years ago, and Smith’s new kidney is still functioning and he is back to his active life, forever grateful to his friend.
“Every night.” he says, “during my nightly prayers with my wife, I thank God for bringing David and Allison to me and for giving me the gift of life. But for David giving me this gift, I would still be in that dialysis chair.”