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Genetic basis of response to immunosuppressive agents, tacrolimus and sirolimus, in renal transplant recipients

Grant number: 14/18871-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2015
Effective date (End): July 31, 2017
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Rosario Dominguez Crespo Hirata
Grantee:Fabiana Dalla Vecchia Genvigir
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

What makes organ transplantation and the patient response to drug therapy especially complex is the nature of the drugs that are used, the number of polymorphic factors that play a role in drug responsiveness and the lack of understanding of the acute and chronic processes that jeopardize organ function and survival. Today, a major goal of immunosuppressive therapy is the individualized treatment in order to decrease acute rejection events, improve efficiency and reduce adverse or toxic effects of drugs. This work aims to contribute to the understanding of the genetic basis of response to immunosuppressive agentes, such as Tacrolimus (calcineurin inhibitor) and Sirolimus (mammalian target of rapamycin inhibitor) used in renal transplantation. One hundred and sixty patients referred for kidney transplantation among patients treated in the Hospital do Rim e Hipertensao - UNIFESP were selected. These individuals were treated with corticosteroids, mycophenolate sodium and tacrolimus-based immunosuppressive regimen for three months. After that, in a group of patients, tacrolimus was substituted for sirolimus. Polymorphisms of genes involved in the pharmacokinetics and pharmacodynamics will be analyzed by real-time PCR. The results will contribute to the knowledge of pharmacogenetic mechanisms involved in the interindividual variation in metabolism and action of the main immunosuppressive drugs used in renal transplantation and its relationship with graft rejection events. They also will contribute to the achievement of individualized therapy, which is able to reduce side effects and improve both patient and graft survival.