Emory University School of Medicine and Children's Healthcare of Atlanta are teaming up with two university hospitals in California to find new ways to make kidney transplants more tolerable for children.
Emory and Children's will partner with UCLA's Mattel Children's Hospital in Los Angeles and Lucile Packard Children's Hospital at Stanford in Palo Alto for a study of kidney transplants in children.
The National Institutes of Health has awarded the partner institutions a five-year grant totaling approximately $6 million for Clinical Trials in Organ Transplantation in Children (CTOT-C).
In the last decade, doctors have been able to refine the regimens of drugs given to transplant patients. Successful transplantation depends on immunosuppressant drugs to prevent tissue rejection, but the drugs bring multiple side effects such as kidney disease and an increased risk of cardiovascular disease.
"Most anti-rejection drugs were developed in adults and are adapted for children by simply adjusting for weight," says Allan Kirk, MD, PhD, scientific director of the Emory Transplant Center and the study's leader. "But the immune system doesnt grow in parallel with a child's weight. The result is that children are often over-immunosuppressed."
Coordinating work among the three university hospitals will allow the study to encompass a group of patients that spans various demographic groups and national origins, says Dr. Kirk, who is a professor of surgery and pediatrics at Emory School of Medicine, a Georgia Research Alliance Eminent Scholar, and an attending surgeon at Children's Healthcare of Atlanta.
As children mature and are gradually exposed to various environmental stresses, such as viral infections, the set of T cells (white blood cells) they have in their bodies that are able to respond to infections or other outside agents changes.
Part of the CTOT-C program will catalog and define how pediatric kidney transplant patients' T cell repertoires evolve as they get older.
The team plans to develop ways to "fingerprint" the pediatric patients' immune systems with information on which genes are turned on and off in their white blood cells. With that information as a diagnostic tool, therapy could be tailored to an individual child at a given point in time, Dr. Kirk says.
"The good news is that outcomes in kidney transplantation have become much more successful in the last couple of decades," says Barry Warshaw, MD, chief of pediatric nephrology at Children's Healthcare of Atlanta and associate professor of pediatrics at Emory. "The bad news is that kidney transplants still don?t last a lifetime."
Dr. Warshaw says one of the key aims of the clinical studies will be to develop a simple blood or urine test to inform doctors whether kidney rejection is "revving up," possibly avoiding painful biopsies.
"We're very excited about this grant and expect that it will one day be seen as a landmark in pediatric renal transplantation," he says.
Before coming to Emory in 2007, Dr. Kirk served as chief of the Transplantation Branch at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health.
His research seeks to achieve immune tolerance of organ and tissue transplants without the use of toxic immunosuppressant drugs. While at the NIH, he served as principal investigator on ten clinical trials leading to advances, including the first trial to investigate a co-stimulation inhibitor in human transplantation and the first trial to investigate the drug alemtuzumab in transplantation in North America.
The Emory Transplant Center and Children's Healthcare of Atlanta perform between 35 and 40 pediatric kidney transplants per year, one of the largest volumes in the United States.
For more information about the Emory Transplant Center, visit http://www.transplant.emory.edu
For more information about Children's Healthcare of Atlanta, visit http://www.choa.org.