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Gene mutation increases drug toxicity, rejection risk in pediatric kidney transplants
Date:2/18/2009

that can put patients at higher risk for infections. In some instances, patients have to be taken off the drug or have their dosage reduced to the point where they risk rejection of the new organ.

The current study analyzed 38 children who had received kidney transplants. Sixteen of the children experienced adverse side effects from MMF therapy. In the adverse reaction group, nine children with the specific UGT point mutation developed leukopenia. The researchers found no strong association between UGT gene variants and diarrhea the most common side effect linked to MMF suggesting gastrointestinal reactions to the drug may be caused by other factors.

Some previous studies have linked UGT gene mutations and MMF-related side effects in kidney transplant recipients, while others have suggested a greater risk for adverse events in children. A review of earlier research combined with their current data led researchers in this study to conclude that pediatric kidney transplant recipients on MMF therapy have a significantly higher likelihood of drug-related complications than adult patients. One previous study compared 22 pediatric and 37 adult transplant recipients, all who started with the standard recommended doses of MMF. Among the children, 54.5 percent experienced adverse side effects compared to 21.6 percent of the adults.

Besides the UGT1A9-331 point mutation, other studies have also linked a second variation, called UGT2B7-900, to possible MMF overexposure and development of leukopenia, said Tsuyoshi Fukuda, Ph.D., co-author on the current study and a colleague in Dr. Vinks' division at Cincinnati Children's. The research team recently completed pharmacokinetic and biomarker studies which analyze how the body metabolizes a drug to solidify the connection between different variants of UGT and MMF overexposure in pediatric kidney transplant patients.

Researchers want to use data from these pharmacokinetic studies as a basis
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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