Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial

Abstract

Background. Although mammalian target of rapamycin inhibitors (mTORi) are associated with a lower incidence of the first episode of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving calcineurin inhibitors (CNIs), the efficacy and safety of the conversion from the antimetabolite to an mTORi for the prevention of CMV recurrence are unknown. Methods. In this single-center prospective randomized trial, low-immunological-risk, CMV-positive kidney transplant recipients receiving preemptive therapy were randomized to be converted (sirolimus [SRL]) or not (control [CTR]) immediately after the treatment of the first episode of CMV infection/disease and were followed for 12 mo. A sample size of 72 patients was calculated to demonstrate a 75% reduction in the incidence of CMV recurrence (80% power, 95% confidence level). Results. Of 3247 adult kidney transplants performed between September 13, 2015, and May 7, 2019, 1309 (40%) were treated for the first CMV infection/disease, and 72 were randomized (35 SRL and 37 CTR). In the SRL group, there were no episodes of CMV recurrence, compared with 16 patients in the CTR group (0% versus 43%; P < 0.0001). Four patients had a second and 1 a third recurrent CMV event. Three of them were converted to SRL and did not develop any further CMV events. There were no differences in the incidence of acute rejection, drug discontinuation, kidney function, and patient and graft survival at 12 mo. Conclusions. These data suggest that, in CMV-positive kidney transplant recipients, the conversion from an antiproliferative drug to SRL after the first CMV episode is an effective and safe strategy for recurrent episodes.

Adverse Drug Events after Kidney Transplantation

“…In a recent single-center prospective randomized trial conducted by Viana et al with a 12-month follow-up, 72 kidney-transplant recipients who had undergone treatment for a first episode of CMV infection/disease either were maintained on the same treatment (antiproliferative agent plus CNIs) or had the antiproliferative replaced with sirolimus. The study found that CMV recurrence occurred in 43% of patients in the control group, whereas the sirolimus group had no recurrence (p ≤ 0.0001) [85]. In de novo kidney-transplant recipients, avoiding CMV infection/disease can be achieved to some extent by replacing the antiproliferative agent (mycophenolic acid) with everolimus [19,86].…”

Advances in the regulatory mechanisms of mTOR in necroptosis

“…Despite preclinical experiments confirming the role of mTOR inhibitors in a variety of diseases, most clinical trials focus on their application in organ transplant as a potent immunosuppressant. In terms of graft-versus-host disease (GVHD) prophylaxis, the addition of sirolimus to standard therapy is propitious to reducing the incidence and severity of graft-versus-host disease (GVHD) and improving the life quality in kidney transplant recipients ( 241 , 242 , 254 , 255 ). Additionally, everolimus improves the prognosis of liver or heart transplants with fewer adverse effects ( 256 , 257 ).…”

New Perspectives in Cytomegalovirus After Transplant: The Role of Immunosuppressant Management

“…In the current issue of Transplantation , Viana et al 7 demonstrate that the conversion from an antimetabolite to mTORi after the treatment of the first episode of CMV was effective in preventing recurrent episodes of CMV in CMV-seropositive KTRs. In this single-center, prospective trial, all adult CMV-positive KTRs who developed the first episode of CMV infection or disease within the first 6 mo after transplantation were randomized to be converted to sirolimus (SRL) or not (control group) immediately after the treatment of the CMV event.…”