More than 60 years after the world’s first successful human kidney transplant was performed at Brigham and Women’s Hospital (BWH), nephrologists at BWH continue to pioneer methods for protecting the integrity of transplanted kidneys and improving outcomes for kidney transplant recipients by proactive management of a potentially devastating viral infection.
Despite the best efforts of clinicians and researchers, one of the greatest challenges to preserving a transplanted kidney over the last several decades has been the BK polyoma virus (BK), named after the patient from whom it was first isolated in 1971. The virus is commonly acquired in childhood, possibly through upper respiratory tract infections.
“We probably have as much expertise treating BK at the Brigham as any center in the world. Because therapy tends to be highly individualized in these patients, it’s very important to get a team with significant experience in dealing with this,” said Anil K. Chandraker, MD, FRCP, Medical Director of Kidney and Pancreas Transplantation at BWH and President of the American Society of Transplantation.
In most people with a normal immune response, the virus is of no consequence. Generally the virus becomes dormant and stays within the body in the kidney epithelial cells. The virus has a steroid-responsive element on its surface, so when steroids are administered for immunosuppression in organ transplant recipients, these drugs act as a growth factor for the virus.
“In kidney transplant recipients, a constellation of factors, including a restriction of blood supply to the kidney (ischemic injury) at the time of transplant, immunosuppressive drugs, and an immune response to the allograft can allow the virus to reactivate and replicate rapidly resulting in ‘BK nephropathy’,” Dr. Chandraker explained. BK nephropathy is marked by poor kidney function, formation of excess connective tissue (fibrosis), and kidney dysfunction or, in too many cases, loss of the organ’s ability to provide sufficient kidney function to avoid dialysis.
“That’s the situation we were in about 15 years ago. If a patient got infected we could not effectively eliminate the virus and there was no specific therapy that could target the virus. When the virus was detected late, there was a 50 percent chance of losing the transplanted kidney within 12 months,” Dr. Chandraker said.
Dr. Chandraker was senior investigator on a randomized, placebo-controlled, double-blind clinical trial investigating whether a 30-day course of levofloxacin, a quinolone-class antibiotic, could significantly reduce viral load and improve function of the transplanted kidney in patients with BK viremia. (CJASN 2014. 9;3: 583-589). Previous work, including laboratory studies and single-center in vivo analyses had suggested that fluoroquinolones such as levofloxacin had antiviral action.
But as the trial showed, blood levels of the virus at three and six months of follow-up were not affected when patients who received levofloxacin were compared to those who received placebo. In addition, analysis of serum creatinine levels over time showed no differences in transplanted kidney function between the two groups during the study period.
“The question then was, what do you do now if you have one of these patients who has BK?,” Dr. Chandraker said.
In 2014, Dr. Chandraker was a founding member of the New England BK Consortium (NEBKCON), in collaboration with colleagues at other Boston transplant centers. The Consortium now includes all 14 transplant centers in New England, the United Network for Organ Sharing (UNOS) region 1.
“We now have a forum where representatives from each center meet three times a year and present difficult cases, and we have also agreed to adopt a standard screening protocol for BK virus across all centers,” he noted.
At the 2016 annual meeting of the American Transplant Congress, Dr. Chandraker and colleagues presented a scientific poster (Am J Transplant. 2016: [suppl 3]) showing that prior to establishing the consortium, there was wide variation in BK screening practices, with no two centers having the same protocol. Some centers screened urine, and others screen plasma, while timing and duration of screening also varied widely.
But under NEBKCON, participating centers will soon implement uniform screening and management protocols based on consensus guidelines, and they plan to standardize testing parameters as well. The use of a uniform protocol is expected to improve patient care and provide investigators with more accurate information about the incidence and prevalence of BK nephropathy in the transplant recipient population, as well as insights into more effective methods of prevention and treatment.
Using the power of pooled data, NEBKCON members will be able for the first time to take part in collaborative clinical trials that are adequately powered to detect conditions, treatment effects, and adverse events that may occur in only a small proportion of transplant patients.
“In a way, this collaboration is just as exciting as doing a clinical trial,” Dr. Chandraker said.
At Brigham and Women’s Hospital, our specialists are available for timely consultations and will work with you to develop a treatment plan for complex cases. Our Physician Liaison Ellen Steward can provide direct assistance with patient referrals and consultations. Ellen can be reached at (617) 582-4733 or esteward@partners.org.
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