Though kidney transplantation can mean the difference between life and death, the procedure is not without significant risk. Associate Research Scientist Simon Lacey, Ph.D., is working to protect transplant patients from one very significant threat.
Kidney transplantation requires that the recipient ‘s immune system be suppressed. Without immune suppression, the recipient ‘s body likely will reject the donor ‘s selfless gift.
Unfortunately, suppressing the organ recipient ‘s immune defenses also leaves the door open for opportunistic infection by pathogens that spring into action at the first sign of weakness.
Lacey and his colleagues in City of Hope ‘s Laboratory of Vaccine Research are beginning a clinical trial to help reduce the threat of one such agent—BK virus (BKV). The virus is responsible for as much as 4 percent of all failed kidney transplants, but incidence of the virus is on the rise due to the use of more potent immunosuppressive drugs in recent years.
The increasing demand for kidney transplants due to the current epidemic of obesity and diet-linked type 2 diabetes is further exacerbating the problem, according to Lacey.
First isolated from a kidney transplant patient in 1971, BKV is found in approximately 85 percent of adults. “We believe it ‘s transmitted early in childhood,” said Lacey, citing some of the naïve and less-than-sanitary activities of children. “But it normally causes no symptoms,” as a healthy immune system easily holds it in check, he said.
However, the immune suppression from anti-rejection medication unleashes BKV in some transplant patients, and “about half of these patients will lose their transplanted kidney to damage caused by the virus,” said Lacey. “In extreme cases, the surgeon may find just a shriveled, blackened lump.”
The best defense is to dial down the doses of anti-rejection drugs. “There currently is no good treatment except reduction of immune suppression, which may lead to [transplant] rejection,” said Lacey. “[They ‘re] between a rock and a hard place.”
BKV also can cause irritation of and bleeding from the lining of the bladder in bone marrow transplant patients. Called hemorrhagic cystitis, the condition can hinder a patient ‘s recovery following transplant, and in rare cases can be life-threatening.
Lacey and his colleagues want to understand how the immune system in healthy people protects them from BKV disease, and how this protection is compromised in some patients. “We would like to be able to develop specific tests to identify people at risk and help clinical management,” he said.
Toward that end, Lacey is beginning a clinical study through the General Clinical Research Center at City of Hope, collecting blood and urine samples from healthy volunteers. They will conduct immunological tests on these samples to characterize immunity to BKV in healthy people. The results will allow them to compare this healthy, protective immunity to the situation in both kidney transplant recipients who are at risk of losing the donated organ due to BKV disease and to other recipients who do not develop BKV disease.
The pending clinical trial builds on work supported by a National Cancer Institute R21 grant. Results of these preliminary studies, done in conjunction with Research Fellow Wendi Zhou, M.D., Ph.D., and Madeva Sharma, research associate, currently are in press in the scientific journal Virology and in the September 2005 issue of the Journal of Virology.
Lacey also has submitted new grant applications proposing to build further on this work and study immunity to BKV in kidney transplant recipients in collaboration with several transplant centers in the United States.
“Perhaps one day we can develop a vaccine to protect those who need it most,” he said.
Information about Lacey ‘s study is available by calling 626-256-4673, ext. 60102.
