A Randomized Clinical Trial on Combination Use of Sirolimus and Tacrolimus in Renal Transplant: A De novo Immunosuppression Approach

Abstract

Background: With the introduction of new immunosuppressive agents like Sirolimus (SRL), we could increase long term allograft survival and decrease the use of other agents like calcineurin inhibitors. SRL in combination with other immunosuppressive medications like calcineurin inhibitors can lead to increase graft function and produce better long-term outcomes. Methods : We enrolled 40 kidney transplantation recipients in trial and followed them up for a duration of 6 months in Shahid Labbafinejad Medical Center. These patients were assigned to receive Tacrolimus (TAC) in combination with Mycophenolic acid or SRL, along with glucocorticoids. All kidney transplant recipients were followed up for serum creatinine and glomerular filtration rate and also complications during therapy. Results : There were no significant differences between the two treated groups regarding serum creatinine level ( p -values = 0.075). However, glomerular filtration rate was significantly increased in SRL group than the other one ( p -values = 0.023). There was no difference between the number of biopsies performed in the two treated groups. In biopsies that were done, in TAC/Mycophenolic acid group, acute antibody mediated rejection in four patients and in SRL/TAC group, acute cellular rejection in two patients were reported. Total cholesterol level was significantly increased in patients who received SRL ( p -values = 0.002). Other side effects were not significantly different in two arms. Conclusions : Our study demonstrated that SRL in the immunosuppressive regimen of kidney transplant recipients in de novo approach lead to better renal function. The long-term outcomes of de novo SRL utilization in kidney allograft recipients should further be assessed. Trial registration: The trial was retrospectively registered in the Iranian Registry on Clinical Trials ( www.irct.ir , registration code: IRCT20160412027346N6), by the date of 04/30/2019. ( https://www.irct.ir/trial/22416 ) Key words : Kidney transplantation, Immunosuppressive Agents, Mammalian target of rapamycin, Calcineurin Inhibitors, Graft Rejection, Sirolimus, Tacrolimus.