A family member, a loved one, or just a Good Samaritan who contemplates donating a kidney naturally wants to know what the effect may be on his or her own long-term health. Although many studies have attempted to address this pressing question, there are few first-rate data, according to researchers speaking at the American Transplant Congress in Boston. And although several new studies are under way to address the deficiencies of the past, even these studies are rife with problems, and definitive results may not be available for years, if ever. “We need better information in this area,” according to Amit Garg, MD, PhD, of London Health Sciences Center in Ontario, “but there are many challenges to getting it.”
“It is only in the last 10 years that there has been enough activity to support large, long-term studies,” he said. Even still, most studies have been of questionable utility. Single-center studies tend to have uniform data but are too small to enable meaningful conclusions to be drawn. Multicenter surveys tend to suffer from a high degree of variability in practices between centers, especially across international borders. Retrospective studies have the potential for selection bias, whereas prospective studies, as others have detailed, have been hampered by the ability to recruit and retain control participants for very-long-term follow-up.
Didier Mandelbrot, MD, medical director of the living kidney donor program at Beth Israel Deaconess Medical Center in Boston, noted that the need for living donors arises from the huge disparity between the need for kidneys and the supply. In addition, living donation has several benefits for recipients, including minimal waiting time (versus an average of 3–5 years for a kidney from a deceased donor), reduced need for dialysis, longer survival of the graft, and longer survival of the patient. Of the 15,000 kidney transplants in the United States every year, about 6000 are from living donors; more than 90,000 living donor transplantation procedures have been performed over the past 20 years.
A 2009 study in the New England Journal of Medicine indicated that the long-term survival of donors was no different from that of matched control individuals, but some questions have remained about the adequacy of the control in this study.
A critical unanswered question, Mandelbrot said, is who is an acceptable living donor? Should the decision hinge on kidney-specific factors, such as creatinine clearance? What else must be considered? “I think it is fair to say there are no long-term data to guide us,” he said. The effects of donation are better known for the most typical donors—young, healthy, white persons—“but what are the long-term outcomes in more borderline patients?”
One potential source for information might be follow-up data kept by the United Network for Organ Sharing, the organization that manages donations in the United States. But there is a steep dropoff in the percentage of donors seen postoperatively over time, with fewer than half returning at 1 year and only 7 percent at 5 years.
An attempt to overcome this lack of information is under way with the Kidney Donor Outcomes Cohort (KDOC) study (www.kdocstudy.com). KDOC is a prospective study that will assess living donors for psychological, social, functional, surgical, and medical outcomes. As of May 2012, the study has enrolled 74 of a planned 280 donors. Enrolling healthy control individuals has been more of a challenge, Mandelbrot said.
Other studies have faced different challenges. Alan Leichtman, MD, of the University of Michigan, described the Renal and Lung Living Donors Evaluation (RELIVE) study, a joint effort among several national kidney transplant centers. Earlier iterations of the study were retrospective or cross-sectional, whereas the current one is prospective. The goal is to assess outcomes in almost 9000 donors over time, combining information from multiple datasets, including transplant center records, Medicare and Medicaid records, the National Death Index, and, for control individuals, the National Health and Nutrition Examination Survey (NHANES).
Much of the work has been resolving discrepancies among the sets. “It is an enormous amount of work,” Leichtman said. The payoff is that the comprehensiveness of the approach “should allow a high probability of accurately estimating the frequency of common postdonation events.”
Bertram Kasiske, MD, professor of medicine and head of transplant nephrology at the University of Minnesota, reported on the Assessing Long-term Outcomes after Living Kidney Donation (ALTOLD) study. This prospective trial, at eight sites in the eastern and central United States, aimed to enroll 200 donors plus paired control individuals, with a 36-month follow-up. “We were perhaps a bit naïve. We wanted to look at living unrelated donors, and find controls through siblings,” but that proved too challenging. “We gave up being purists,” he said. The researchers expanded their enrollment to include any living donors and nonsibling control individuals.
After 6 months, their original 204 donors had dropped to 198. Currently, they have 80 percent of the original cohort out to 24 months.
Given the enormous challenges, expense, and difficulties of conducting such long-term studies, one audience member suggested, “Perhaps we are trying to achieve something we can never achieve.” Instead, perhaps the focus should be on teaching donors to understand that any increase in risk is likely to be quite small and to help them find healthy ways of dealing with the inevitable uncertainty after their generous gift.
Mandelbrot offered some support to that idea. “We may have to accept the fact that we will never know what we want to know,” he concluded—that is, how donors do over the very long term. “We may have to accept there will always be uncertainty.”
Leichtman countered that there was no reason to accept the fatalism of that view. “It would be a shame if, 50 years from now, we were still bemoaning that we didn’t have the data,” he said.
