New Procedure Allows Kidney Transplants From Any Donor
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 Wednesday 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 eight years than patients who had remained on waiting lists or received a kidney transplanted from a deceased donor.
这项周三（3月9日）发表在《新英格兰医学杂志》(The New England Journal of Medicine)上的新研究称，医生们成功地改造了患者的免疫系统，使得他们可以接受配型不合的供体肾。8年后，这些患者的存活率显著高于仍在排队等待移植或接受了已故供者肾移植的患者。
The method, known as desensitization, “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.
宾夕法尼亚大学佩尔蒙医学院(University of Pennsylvania’s Perelman School of Medicine)的肾病专家，美国肾脏病基金会(National Kidney Foundation)主席杰弗里·伯恩斯(Jeffery Berns)说，这种被称为“脱敏”(desensitization)的方法“有望挽救许多人的生命”。
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, Mr. 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 percent are so sensitive that finding a compatible organ is all but impossible. In addition, said Dr. Dorry Segev, the lead author of the new 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.
研究人员估计，在美国排队等待肾移植的10万名患者中，有约一半带有会攻击移植器官的抗体，有约20%的人非常敏感，以至于几乎不可能找到匹配的器官。此外，这项新研究的主要作者，约翰斯·霍普金斯大学医学院(Johns Hopkins University School of Medicine)的移植外科医生多莉·塞格夫(Dorry Segev)博士说，还有数目不详的肾功能衰竭患者在得知他们的身体会排斥基本上所有的移植器官之后，干脆放弃了等待移植，将就地去接受透析——一种帮人排出体内多余水分的费事做法，一旦接受透析，患者的整个生活几乎都将受制于它。
Desensitization 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, Dr. 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 desensitization is cheaper in the long run than dialysis, which costs $70,000 a year for life.
Although by far the biggest use of desensitization 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 desensitization, “but it’s certainly possible if there are known incompatibilities,” Dr. Segev said. With lungs, he said, desensitization “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 centers 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 percent of those who received an incompatible kidney were still alive, compared with 62.9 percent who remained on the waiting list or received a deceased donor kidney and 43.9 percent who remained on the waiting list but never got a transplant.
The desensitization 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, Dr. 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 Dr. Krista L. Lentine, the medical director of the living donation program at the Saint Louis Center for Transplantation, but patients often still cannot find a compatible organ because they have antibodies that would reject almost every kidney. In those cases, “desensitization may be the only realistic option for receiving a transplant,” said Dr. Lentine, who was not involved with the study.
该方案有可能成功，圣路易斯移植中心(Saint Louis Center for Transplantation)活体捐赠计划的医务主任克里什陶·L·朗坦(Krista L. Lentine)博士说，但很多时候，患者仍然无法找到匹配的器官，因为他们体内的抗体会令他们排斥几乎所有的肾脏。在这种情况下，“脱敏恐怕是想要移植者的唯一现实选择”，朗坦博士说道。她并没有参与前述新研究。
Dr. Jeffrey Campsen, a transplant surgeon at the University of Utah Health Sciences Center 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.
犹他大学健康科学中心(University of Utah Health Sciences Center)的移植外科医生杰弗里·坎普森(Jeffrey Campsen)博士也没有参与该研究，他表示他团队的工作以交换移植方案为主，并已经取得了相当的成功。但他也遇到过患者的供者不愿意参与交换的情况。“如果供者与患者之间存在感情纽带，就会造成障碍，”他说。
The new data showing the success of desensitization “lets people get behind it,” Dr. Campsen said, adding, “I do think it is something we would consider.”
Mr. Smith, the New Orleans patient who went through desensitization, 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 six and a half 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.
新奥尔良的患者史密斯先生接受了“脱敏”治疗。他患有退行性肾病(progressive kidney disease)，病魔慢慢地侵蚀他的肾脏，令它伤痕累累，以致在2004年彻底失去了功能。他的嫂子艾莉森·萨顿(Allison Sutton)给他捐献了一个肾，但遗憾的是，六年半之后，移植还是失败了。他只好继续接受透析，每周四天里都有数小时困在透析机上。他告诉朋友们，虽然保住了命，但这种日子根本不算是“生活”。
Then a nurse suggested that he ask Johns Hopkins about its desensitization 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, Mrs. Smith was talking on the phone to a college friend, Angela Watkins, who lives in Augusta, Ga., and mentioned that Mr. Smith was praying for a donor. Mrs. Watkins’s husband, David Watkins, a judge in state court, had been friends with Mr. Smith in college and the two wives, also college friends, had kept in touch over the years.
有一天，史密斯夫人在跟大学时的朋友，住在佐治亚州奥古斯塔的安杰拉·沃特金斯(Angela Watkins)通电话时提到了史密斯先生期待能找到一个供者。沃特金斯夫人的丈夫戴维·沃特金斯(David Watkins)是州法院的法官，他跟史密斯先生在大学时代是朋友，两位妻子也一样，而且她们多年来一直保持着联系。
Mrs. Watkins told her husband about the conversation, and they asked themselves if they should offer to donate.
“We talked and researched and prayed,” Judge 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.
Mr. Smith warned his old friend that donating was an enormous undertaking. “He said, ‘You can’t grasp what you are doing.’ I heard him but it didn’t register,” Judge Watkins said. “I told him, ‘I have something you need, so what’s the big deal?’ ”
Of course, it was a big deal. Although Judge Watkins had prepared by getting himself in top physical shape, it still took about six months to recover from the operation.
That was four years ago, and Mr. 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.”