By measuring just three genetic molecules in a urine sample, scientists were able to detect whether transplanted kidneys were in the process of being rejected, as well as identify patients at risk for rejection weeks to months before showing symptoms.
The study, published in The New England Journal of Medicine, was co-authored by 25 investigators from across the country, including John Friedewald, MD, associate professor in medicine-nephrology and surgery-organ transplantation, and Michael Abecassis, MD, MBA, director of the Comprehensive Transplant Center and chief of surgery-organ transplantation.
The urine test accurately diagnoses acute rejection of kidney transplants, the most frequent and serious complication for this surgery, and may help physicians fine-tune the amount of powerful immunosuppressive drugs that organ transplant patients must take for the rest of their lives.
The clinical trial began in 2006 with participation from five medical centers, including Northwestern University Feinberg School of Medicine, which contributed the most transplant patients.
Researchers collected 4,300 urine specimens during the first year of transplantation, starting three days after surgery. Analysis of the samples revealed the accuracy of the three-gene biomarker. The scientists used biopsy to confirm rejection.
“Our work on this trial led to our being funded in the next round of Clinical Trials in Organ Transplants funding,” Friedewald said. “We currently are the lead site on two similar trials and are in the process of enrolling 300 kidney and liver patients to advance the findings from the recently published results.”
In those trials, Feinberg scientists will look at blood and biopsy tissue in addition to urine samples for improved biomarkers of rejection and other problems in kidney and liver transplant recipients.
“The hope of the current publication and our ongoing National Institutes of Health-funded research is to improve non-invasive testing for transplant recipients and to be able to better individualize therapy for our patients,” Friedewald said.
The New England Journal of Medicine study was supported by NIH grants UO1AI63589 and R37AI051652, the Qatar National Research Foundation (NPRP 08-503-3-111) and by a Clinical and Translational Science Center Award (UL1TR000457, to Weill Cornell Medical College). From September 2004 through August 2011, Northwestern was a consortium site on the U01 AI063589 grant.