Early conversion of tacrolimus to everolimus in renal transplant recipients

• Grant number: 12/11910-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2012
• Effective date (End): September 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Fernanda Cordeiro de Carvalho
• Grantee: Gustavo Gonçalves Yogolare
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Over the past decade, despite significant progress in rejection rates and one-year graft survival after kidney transplantation, five-year graft survival has shown little improvement. This is partially due to nephrotoxicity secondary to calcineurin inhibitors, which have been routinely used in transplantation practice and frequently lead to chronic graft injury. Thus, alternative strategies have been investigated. Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, are the most recently available immunosuppressant agents. Because they lack nephrotoxicity, these drugs seem to be a promising therapeutic alternative for the treatment of chronic graft injury secondary to calcineurin inhibitors. Nonetheless, as these immunosuppressants have been associated with an increased rate of acute rejection their use is not recommended in the first months following transplantation several studies have shown that switching calcineurin to mTOR inhibitors is safe, and efficient in improving renal function. However, there is no consensus as to when switching should occur. Early switching attenuates the nephrotoxic effects of calcineurin inhibitors but increases the risk of rejection. Late switching, in turn, reduces the risk of rejection but increases the length of exposure to calcineurin inhibitors and the adverse effects secondary to nephrotoxicity. The purpose of this study is to assess early switching (3 months after transplantation) from tacrolimus to everolimus in kidney transplantation recipients.(AU)