Pharmacokinetics of Micofenolato Mofetil in combination with Tacrolimus and Everolimo in kidney transplant patients

• Grant number: 20/13282-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2021
• Effective date (End): March 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carlucci Gualberto Ventura
• Grantee: Flávia Armiliato Albuquerque
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/19339-9 - A prospective, single center, randomized study comparing the efficacy and safety of the addition of everolimus to tacrolimus/mycophenolate mofetil/predinisone in kidney transplanted recipients HLA-sensitized, AP.TEM

Abstract

The number of kidney transplants performed in sensitized patients has increased recently, reaching about 28% of kidney transplantation in our center. The incidence of acute antibody-mediated -rejection (AMR) under standard triple therapy (Tacrolimus, Mycophenolate Mofetil, and Prednisone) has been elevated in this population. The idea of evaluating the effectiveness of adding a fourth immunosuppressant (Everolimo), a quadruple immunosuppressive regimen, will be tested in order to analyze its impact on the acute antibody-mediated rejection rates. Great variability in inter-individual absorption and metabolism, as well as the interaction between immunosuppressants, makes drug monitoring an essential tool to maintain these drugs in the therapeutic window. The aim of the present study will be to analyze the levels of mycophenolic acid (MPA) with or without the association with Everolimo, in the first 6 months after kidney transplantation. Thirty patients will be enrolled, 15 in the control group (mycophenolate, tacrolimus) and 15 in the study group (mycophenolate, tacrolimus, everolimus). All patients will receive corticosteroids and induction with Thymoglobulin. The concentration monitoring of mycophenolic acid (MPA) will be performed at 7, 14, 21, 30, 60, 90, and 180 days after kidney transplantation through the calculated area under the curve, using trough (C0) and 2 hours after oral administration (C2) measures. The levels of Everolimo and Tacrolimo also will be analyzed concomitantly, through the basal blood measures (C0). The glomerular filtration rate of the two treatment groups will be compared by calculating the MDRD (mL/min) at 7, 30, 60, 90, and 180 days after transplantation.(AU)