Stanford Report, January 17, 2001
|Best transplant outcomes
achieved when children receive kidneys from adults
Placing a kidney from an adult donor into an infant or young child not only improves recovery prospects, it produces the best survival rates of any transplanted organ in any age group, according to a study by Stanford medical researchers.
Oscar Salvatierra, MD, professor of surgery and nephrology and director of kidney transplantation at Lucile Packard Children's Hospital, said that until now the gold standard has been transplantation between 19- to 45-year-old siblings with identical immune systems.
However, Salvatierra and his collaborators demonstrated in their study that adult-sized kidneys transplanted into infants and young children do better than this standard, particularly after the first year. The study was published in the Dec. 27 issue of Transplantation.
The best results came with kidneys from living donors, particularly when the donor was one of the child's parents. Adult cadaver kidneys were less optimal but even they succeeded at least as well over the long term as living-donor transplants to adult recipients.
These findings appeared not only in patients treated at Packard, but also in data from the Scientific Renal Transplant Registry maintained by the United Network for Organ Sharing, or UNOS, which includes all transplant procedures performed in the United States.
"As long as the adult kidney functions immediately in the child, there is no kidney loss from irreversible acute rejection after the first year," Salvatierra said. "The challenge then becomes keeping the kidney functioning through the first year. Once the patient gets past that milestone, then the kidney is going to do very well."
Adequate blood flow is key. The child's smaller heart, blood volume and vessels are insufficient to satisfy the blood-flow demand of an adult-sized kidney, posing the risk of malfunction if blood clots develop in the kidney.
In previous research, Salvatierra and his colleagues determined how much blood flow is needed to support a transplanted adult kidney in a child and developed a way of supplying it. By placing the child on intravenous and gastric-tube fluids, venous pressure is raised during surgery. Blood volume is then increased for at least six months following the transplant. With this method, every adult-to-child kidney transplant patient at Packard has survived the first year.
Minnie M. Sarwal, MD, PhD, a molecular biologist and assistant professor of pediatric nephrology, collaborated with Salvatierra on the study. She has considered why the larger, adult-size kidney would do better in children than organs from donors the children's size.
"The larger kidney confers some kind of immunological privilege. In animal research, transplanting just one kidney between rats without identical immune systems results in rejection unless drugs that suppress the immune response are given. But transplanting two kidneys is successful, even without drugs. Apparently, the larger mass of donor tissue 'exhausts' the recipient's immune system and allows it to tolerate the transplant."
Sarwal is now pursuing experiments to identify this mechanism and use it.
"It is likely that we can reduce the level of immunosuppressive drugs in children receiving adult kidneys after the first year," she said. "My goal is to find a test that tells precisely how much we can reduce immunosuppression and still protect the transplanted kidney from rejection over the long term. That will greatly improve care for these children."
Other co-authors of the study, which was funded by grants from the David and Lucile Packard Foundation and UNOS, include Maria T. Millan, MD, an assistant professor of surgery at Stanford, and J. Michael Cecka, PhD, of the UCLA Tissue Typing Laboratory.