Supported Research

General Audience Summary

Summary: Mycophenolate (or mycophenolic acid) is a commonly used medication for life-long maintenance to prevent the body from rejecting the transplanted kidney. Mycophenolate is usually prescribed in a fixed regimen, and almost all patients would receive the same starting dose. Unfortunately, many patients show large variations and high blood concentrations of mycophenolate, which can result in severe side effects such as reduced white blood cell counts and infection. In many transplant centres in Canada, more than one quarter of the kidney transplant patients develop severe side effects to mycophenolate. The exact reasons why so many patients have high and variable mycophenolate blood concentrations remain unknown. Recently, our lab has found a potential cause: that a blood toxin called "p-cresol" which is accumulated in this patient population may be the culprit of the high blood concentrations and the toxic responses observed of mycophenolate. Using innovative human test tube models, we found that p-cresol reduced the body's ability to eliminate mycophenolate, therefore effectively pushing up its blood levels. As the blood concentrations of p-cresol are also highly variable, p-cresol could be one of the major reasons for the large variation observed of mycophenolate blood levels in patients. Our clinical experiment will confirm our thinking in adult kidney transplant patients where we will compare the blood concentrations of both p-cresol and mycophenolate, using cutting edge approaches in our field. If we are correct, health care professionals can actively manage (i.e. reduce) the blood levels of p-cresol (e.g. through diet regimens or synbiotics) which should significantly reduce the chance of developing mycophenolate-associated side effects. Due to reduced variations (or uncertainties) in mycophenolate dosing, the patient's overall experience to mycophenolate will also be improved. This study directly addresses the vision and mission of the Kidney Foundation of Canada by improving the health of the transplanted kidney and the quality-of-lives of our patients through innovative research.