For many adult kidney transplant patients, the anti-rejection drug mycophenolic acid is a literal life-saver — but it’s also unpredictable. If the dose is too low, the body rejects the new organ; too high, and the drug becomes toxic.
Until now, it was not understood why the same dose affects individual patients so differently.
Now, a team of researchers at the University of Alberta has pinpointed “uremic toxins” — natural bodily waste products that build up when the kidneys are not working well.
In a recently published paper, the team demonstrates its population-level model based on 283 blood samples from 41 patients, showing that different toxins alter the impact of mycophenolic acid in the body in different ways.
They identify one particular toxin called p-cresol sulfate as a key factor in increasing the exposure of mycophenolic acid.
“Understanding these specific toxin interactions will allow us to develop more tailored dosing guidelines for transplant patients,” says principal investigator Dr. Tony Kiang, associate professor in the Faculty of Pharmacy and Pharmaceutical Sciences.
“This discovery paves the way for personalized, precision-dosed medicine that could dramatically lower organ rejection rates and drug side-effects.”
Kiang plans additional investigations to understand the clinical impacts of the identified toxin-drug interactions in this population.
This research was funded by The Kidney Foundation of Canada.