Stanford Report, May 30, 2001
|New drug approach avoids
side effects in children receiving kidney transplants
Young kidney transplant patients no longer must endure a myriad of unpleasant, medication-induced side effects -- thanks to a new drug protocol developed by researchers at Stanford University Medical Center. Early results show the new regimen causes fewer side effects than current anti-rejection medication, and may actually promote improved function in the transplanted organs.
Results of the Stanford study on the new drug protocol were presented by co-researchers Minnie Sarwal, MD, PhD, and Oscar Salvatierra, MD, at the recent combined meeting of the American Societies of Transplantation and Transplant Surgeons.
Salvatierra, professor of pediatrics and surgery and director of the pediatric kidney transplant program at Lucile Packard Children's Hospital, said steroids have been used to prevent the rejection of newly transplanted organs for more than 40 years. "Transplant surgeons use steroids because they can suppress the immune system and keep it from attacking the new organ as an invader," he said. "The side effects, though, pose a real problem -- especially in children."
Steroid use frequently causes acne, an abnormally round, puffy "moon" face and mood swings. It can also lead to hypertension, impaired growth, slow wound healing and elevated blood-fat levels. Sarwal, Salvatierra and other Stanford researchers on the team -- including Steven Alexander, MD, professor of pediatrics (nephrology); Peter Yorgin, MD, assistant professor of pediatrics (nephrology); and Maria Millan, MD, assistant professor of surgery -- believe these side effects may cause looks-conscious adolescents to stop taking the drugs and to suffer organ rejection as a consequence. Adolescents now suffer the most transplanted-organ loss of any age group.
Mindful of the drawbacks of steroids, transplant surgeons tried withdrawing patients from steroids shortly after surgery and reducing the dosages. When the methods backfired -- actually leading to higher-than-normal rejection rates -- the research team realized it might have been taking the wrong approach.
"We began thinking that steroid withdrawal failed because the immune system had become dependent on the steroids and then rebounded when the medication was withdrawn," said Sarwal, a molecular geneticist and assistant professor of pediatric nephrology. With this in mind, the research team decided to forego steroids altogether and turn to alternative immunosuppressive drugs.
The research team developed a regimen consisting of several drugs -- including daclizumab, a monoclonal antibody -- that suppress the immune system but have a lesser effect on the patient. "While steroids affect every tissue of the body, daclizumab only blocks the expression of the immune system," said Salvatierra. "It is a more specific suppressant and consequently has fewer side effects."
The team's study involved putting10 kidney-transplant patients between the ages of 5 and 21 on the drug regimen. The patients have had minimal side effects and have shown excellent results in comparison to a control group receiving steroids. As a result, another 11 patients have been added to the study group.
"It's wonderful to walk into the clinic and see these children look completely normal," Sarwal said. "In the past it was always evident who had been transplanted -- they were short and they had round faces, extra hair and acne. Now you can't tell that these children have been transplanted. They look wonderful and are growing like weeds."
The Stanford researchers suspect that without some of more serious side effects of steroid use -- including hypertension and elevated blood-fat levels -- kidney function will improve over time. They also believe the steroid-free drug protocol should work with transplants other than kidneys and in patients of all ages.
"The kidney is highly immunogenic and children are the most difficult patients," Salvatierra said. "If this protocol continues to prove successful with pediatric kidney recipients, it would have profound implications across the entire field of organ transplantation."
The paper on the steroid-free protocol has been accepted as a rapid communication for publication in the journal Transplantation.
Daclizumab is manufactured
and marketed as Zenapax by Roche.