Cover Story
The New Transplant Patient
Older, sicker patients are becoming eligible for organ transplantation, increasing the need for organs and raising new questions about who should get priority on waiting lists.
By Kate Ledger
Ardell Lien of Caledonia, Minnesota, had a history of heart trouble that started with atrial fibrillation when he was in his 30s; but nothing prepared him for the devastation of congestive heart failure that hit hard a few decades later. The golf-playing, globetrotting father of three, who’d once lived on a boat with his wife, Maureen, could barely walk or take a shower without experiencing extreme fatigue by the time he’d reached his 60s.
Lien’s family and friends encouraged him to go to Mayo Clinic for further evaluation, and there, Lien was surprised to learn that hope still existed. His doctor, Brooks Edwards, M.D., thought Lien would be a good candidate for a heart transplant. “I never thought I’d be eligible for that kind of surgery at age 67,” Lien says. What’s more, Lien remained a candidate even as his kidneys began to fail while he was waiting for a new heart.
As his health rapidly withered, Lien was moved to tears when he learned that a heart and a kidney had suddenly become available. In January 2003, he underwent a 12-hour double-organ transplant. His recovery astounded his family. Within months, he was reroofing his house. Two years later, at age 69, eager to acknowledge the measures that had saved his life, he embarked on a highly publicized solo trip around the world by 27-foot sailboat. The amazing feat (only a handful of individuals have ever circumnavigated the globe on their own, and Lien was the first transplant recipient to undertake the arduous journey) enabled him to raise awareness about advances in organ transplantation and the impact of organ donation, as he met with doctors and patient groups at ports around the world.
Now 76 years old and in continuing good health, Lien represents a trend: A growing number of people in their 60s and 70s are eligible for organ transplants. Sicker patients are finding their way onto the waiting list for organs, too.
The ability to perform transplants on such patients is the result of several factors including advances in drugs for immunosuppression and more refined tissue-matching technology. What’s more, as medications for treating chronic diseases have improved, even patients with conditions such as HIV and hepatitis C now may be eligible to receive a donated organ. Although these developments have given a second chance to some patients facing organ failure, they’ve also lengthened the list of people waiting for an organ. “The real limitation we face,” says Timothy Pruett, M.D., chair of the division of transplantation at the University of Minnesota, “is having enough organs.”
Transplantation Comes of Age
Although organ transplantation may once have been considered an extreme or even experimental treatment, it’s taken its place during the last two decades as a mainstream therapy for organ failure. In patients with kidney failure, for instance, it’s been shown to provide better outcomes than dialysis. Consequently, transplants are being offered to more patients today than 10 years ago.
A Question of Supply
Numerous campaigns over the last decade have highlighted organ donation in an attempt to increase the number of people identified as potential donors. Because some of the latest research has shown, particularly in the case of kidney patients, that organs from living donors work even better than those from deceased ones, the push is on to raise awareness about the opportunity—and benefit—of giving a kidney to someone in need. Because not all donors who want to give a kidney to a sick friend or relative are compatible, one of the recent advances in kidney donation is “paired donation,” in which a donor who’s not compatible with the person to whom they wish to give their organ can give the organ to another patient whose donor will, in turn, provide a more compatible organ. More than 260 kidneys have been exchanged in such arrangements. The concept has been so successful that the United Network for Organ Sharing is about to roll out a national campaign for paired donation, hoping to increase awareness of this life-saving option.
Another strategy to increase the number of living donors is the use of “domino” transplants, in which one patient’s diseased organ is given to another patient who can make use of it. For instance, a 50-year-old with familial amyloidosis, a disease in which the liver produces abnormal proteins that accumulate over time and damage other organs, may require a new liver. But the diseased organ may still be usable for a 60-year-old with liver failure. “The donated liver itself will work fine, except for making that abnormal protein, and since it takes decades for that protein to cause damage, it can be a reasonable organ for an older patient to receive,” says Brooks Edwards, M.D., director of Mayo Clinic’s Transplant Center.
Arthur Matas, M.D., director of the University of Minnesota’s renal transplantation program, has posed another idea for increasing the pool of available organs: providing compensation to donors. He believes this may be a reasonable way to make organ donation more compelling and has been speaking about it for several years. Currently in the United States, it’s illegal to provide any compensation for a donated organ. He points out that sperm, plasma, and egg donations do involve payment, “so there’s precedent.” He adds that such a system would have to involve government oversight. But it’s an issue that remains hotly debated. Among concerns about compensation is the disparity between rich recipients who can afford the transplant and impoverished donors. “People get very passionate about the topic,” Matas notes, “on both sides.”—K.L.
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ne reason why transplant medicine has been able to make such strides—and why it has become an option for people like Lien who may once have been ineligible—is the introduction of powerful anti-rejection drugs. A significant milestone took place in 1983 when the immunosuppression drug cyclosporine came on the scene, dramatically reducing organ-rejection rates. Cylosporine and tacrolimus, which was introduced about a decade later, also enabled patients to minimize or avoid steroid treatment after receiving a transplanted organ, reducing subsequent infections and other complications. A handful of other antirejection drugs have since been introduced that allow more specific suppression of the patient’s immune system and cause even fewer side effects. “In the past, as we were giving more broad-spectrum bone marrow suppression to patients, we’d have problems with postsurgical healing. That would limit the type of patient that could withstand surgery,” explains University of Minnesota transplant surgeon Ty Dunn, M.D., who specializes in the treatment of complex patients.
Another milestone was reached in 1994, with the introduction of antiviral medication that reduced postoperative infections. Used in combination with antirejection drugs, the antivirals helped make positive outcomes much more common. “We were able to confidently offer transplants to patients who were a little bit older and a little frailer,” Dunn says.
In fact, these developments prompted institutions that had set age limits for transplant patients to rethink them. Back in 1983, Mayo had determined that the cut-off for being eligible for a heart transplant would be age 65, recalls Edwards. But over the next decade, that number began to look arbitrary. For one thing, it became clear that individual patients age differently and that some older patients were fit for surgery.
In 1993, Mayo removed the age restriction, allowing patients to be considered based on their overall health. Edwards says that if patients maintain muscle mass and bone density, and have excellent liver function and cognitive abilities, Mayo will consider them. “We look more at the physiological age than calendar age,” he says, adding that they probably unfairly excluded some patients in the past because of how old they were. (To date, Mayo’s oldest heart recipient was 73 years old at the time of her surgery, and she’s still going strong six years later at 79.)
Overall, Edwards says, the outcomes for heart transplant patients show that removing the age limit has been reasonable: Mayo’s three-year survival rate for patients younger than 60 is 87 percent; for patients older than 60, it’s 86 percent. What’s been critical, he adds, is that physicians have developed a keener sense over the years of proper patient selection: “We’ve gotten better at selecting patients who have the right stuff, who can withstand the challenges of a big procedure and the commitment to the rehabilitation that comes after it.” In addition, physicians have discovered that older patients, whose immune systems are less robust than younger ones, tend to accept organs better.
A Series of Medical Advances
Over the years, surgical advances have enabled sicker patients to be added to the waiting list for organs as well. Patients with heart failure, for instance, often have problems in other organs such as the kidneys. When Mayo established its transplant center in 1999, it put transplant surgeons and physicians who specialize in disparate organ systems in close proximity to learn from one another. As they gained experience, they began conducting multiple-organ transplants. “We’ve probably performed more combined transplants than anywhere in the country,” Edwards says, noting the center has performed 107 simultaneous liver-kidney transplants, 21 heart-kidney, 21 heart-liver, and one heart-liver-lung transplant.
In fact, combined transplants have been an incredible boon for medically complex, high-risk diabetes patients, points out Dunn. Although they were once excluded from receiving new kidneys because transplant results were so bad, patients with diabetes who receive a combined kidney-pancreas transplant, or a kidney first and a pancreas at a later date, can be free from dialysis and also from diabetes. “That’s a huge advantage when you’re talking about going on life-long immunosuppression,” Dunn says. “Ideally, you don’t want to be diabetic and at risk for infections from immunosuppression at the same time.” She says the university has been doing kidney-pancreas transplants since 1967 and that the outcomes keep getting better. The university has research protocols underway in which diabetic patients with kidney failure can receive a kidney and then a transplant of insulin-producing islet cells to restore the pancreas function they’ve lost.
Some of the most difficult patients to transplant are those who already have antibodies in their system. They’re known as “sensitized” patients, and they have been exposed to foreign human antigens through blood transfusions, previous transplants, or pregnancy and developed the antibodies to them. These antibodies are present in about 30 percent of patients and can present a significant challenge when it comes to finding a compatible donor.
But advances in the last five years have enabled doctors to detect antibody levels much more precisely. In the past, predicting donor compatibility involved some degree of guesswork and the rare-but-catastrophic problem of hyperacute rejection, where within minutes of blood flowing into the new kidney, a patient would mount a rejection response and the organ would fail, was a concern. “It’s so rare now,” Dunn says, “that most of the people who have been trained in the last decade have never even seen hyperacute rejection. Our tissue- typing practices are much more sensitive and specific than ever before. You can actually put names on the different tissue antigens and plan ahead to avoid them when considering a donor.”
And there are now protocols available to help patients who have problematic levels of antibodies. Dunn uses one of several desensitization techniques that can make these patients—an estimated 5 percent of those for whom transplant would have once been impossible—eligible for a new organ. One technique involves giving a sensitized patient high-dose intravenous immunoglobulin (IVIG) to dampen the activity of B cells that produce antibodies. In another, called plasmapheresis, the patient’s blood is removed in order to “wash” away the problematic antibodies, then returned. In addition, antibody-depleting medications are now available. “We deploy these desensitization strategies on a very selective basis,” Dunn notes. “Our bodies have entrenched immune memory responses, and we can’t always predict how effective or durable the desensitation treatment will be.”
One area that is evolving is transplantation in patients with chronic viral infections. “It used to be that one of the huge contraindications for transplantation was being HIV-positive,” Pruett says. “It turns out that with current antiviral drugs, people who have HIV under good control can do well with a transplant.” An article in the New England Journal of Medicine last year highlighted the success of kidney transplants in HIV-positive patients. Recently, federal health officials began pushing for the repeal of the ban on transplanting HIV-positive organs in order to give them to HIV-positive recipients.
Pruett is interested in increasing access to kidney transplantation for people with hepatitis C, who represent between 5 and 10 percent of the population on dialysis. “They’re perceived as being folks who are at higher risk, and it’s clear—only about 1 percent of the people we transplant are hep C positive—they aren’t accessing transplantation as much as might benefit them,” he says. But over the last several years, hepatitis C has been the most common indication for liver transplantation, and through these transplants, doctors have learned more about antiviral drug therapies that can suppress the presence of the virus along with the immunosuppression medications that stave off organ rejection. Pruett believes that knowledge about keeping the viral load in check can be extended to hepatitis C patients who need kidney transplants: “I think we can offer more transplants for people with hep C than we currently do.”
More Patients Need More Organs
The fact that more patients are candidates for organ transplantation means that more organs than ever before are needed to meet the demands. The United Network for Organ Sharing (UNOS), the private, nonprofit organization contracted since 1984 by the federal government to keep a list of potential recipients, has more than 110,000 people on its waiting list for an organ (72,000 of them are considered “active,” meaning they would be physically ready if an organ became available and don’t have another medical complication such as cancer that must be resolved first). The list grows by more than 4,000 patients a month. Delineated regions within the United States maintain their own lists of patients needing organs. (The Upper Midwest region, which includes Minnesota, North and South Dakota, and three counties in Wisconsin, has 2,300 patients on its list. That number increases slightly each year.)
In renal transplantation, the largest area of transplantation with nearly 20,000 surgeries a year, growing demand for kidneys has not only expanded the waiting list but also broadened the types of organs that are deemed usable. Arthur Matas, M.D., director of the University of Minnesota’s renal program, has seen that trend firsthand. “When I saw patients here in 1980, I would tell a patient that if they went on the list for a deceased organ transplant, they’d wait a year—and add to that, we’d only use kidneys from young trauma victims. Now I tell patients they’re going to wait five years and not only do we use kidneys from young trauma patients but we use kidneys from older people who died of strokes. We’re using kidneys we wouldn’t have used back then just because the need has gotten so much greater.”
But even as more people become candidates for transplantation, the fact is for the majority on the waiting list, compatible organs do not materialize in time. Most wait more than five years, and annually more than 6,000 people die waiting for a transplant. “For those of us in the field, that’s devastating,” Pruett says.
Ethical Quandaries
As the field of transplantation continues to evolve, along with strategies that make it possible to transplant organs into older and sicker patients, thorny ethical issues are emerging. “Unlike other life-saving medical interventions, transplantation is a treatment that has built-in limits because we don’t have enough organs for everybody,” notes Mayo bioethicist Barbara Koenig, Ph.D. Those limits have prompted many to wonder whether older and sicker patients even belong on the waiting list for organs.
A recent proposal by UNOS would replace the current kidney allocation system, in which patients receive priority based on the length of time they have been waiting, with one that would more concertedly match younger, healthier organs to younger patients. The idea is to direct the organ to where it will have the best possible chance of functioning the longest.
Some bioethicists have argued that the only way to address the need for hearts, for instance, given the limited supply available, is to decrease demand and make the selection criteria for candidates more stringent. Koenig puts it this way: “It’s not feasible for our society that everybody can have four heart transplants before they die. We need to balance competing goods—helping individuals live longer with concerns about social justice.”
One of the domains that needs to be addressed from a bioethics and a policy standpoint is the increasing age of organ recipients. “Is it reasonable for an older person to have a 20-year-old’s organ that comes available in an accident? Or to ask a 20-year-old to donate a kidney to a parent or grandparent?” Koenig asks. “What is the upper cut-off, and are we going to have one?” She predicts the ongoing tension will increase between the push to do more medically, to do more transplants for higher-risk and older patients, and the consequences of not having enough organs.
But even as the nation sets policy about the allocation of organs, each institution will have to navigate on its own what is medically possible for patients amid parameters that are constantly shifting. “People want everyone to be treated well,” Pruett says. “We’ve learned, for example, that transplantation offers an optimal kind of treatment to help patients live longer. A kidney transplant is cheaper, on a national scale, than dialysis. And a transplant can provide a high quality of life. But we can’t do it for everybody. We just don’t have the resources to do that. So the question becomes, how do we do the best with what we have, and how do we draw boundaries? The answer is that the questions are still evolving, and no one knows for sure right now.” MM
Kate Ledger is a St. Paul freelance writer and frequent contributor to Minnesota Medicine.