Use of mTOR inhibitor as prophylaxis for cytomegalovirus disease after kidney transplantation: A natural experiment

Abstract

Objectives To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR‐inhibitor‐containing immunosuppressive regimen without prophylactic CMV treatment. Methods This single‐center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015‐07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R− CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). Results Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R−, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R−, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [<90 days] EVRd). The incidence of biopsy‐proven acute rejection was 5.6%, and median glomerular filtration rate at month 12 was 47 mL/min/1.73m2. One‐year patient and death‐censored graft survivals were 97.4% and 98.1%. Conclusion This study suggests that everolimus‐containing immunosuppressive regimen reduces the need for preventive strategies for CMV infection in the majority of kidney transplant recipients, reducing antiviral drug‐associated toxicities and healthcare‐related expenditures.

Longitudinal study on oral shedding of human betaherpesviruses 6 and 7 in renal transplant recipients reveals active replication

“…All patients received immunosuppressive therapy and six patients used ganciclovir for treatment of CMV disease, consisted of intravenous 5 mg/kg b.i. d. ganciclovir, adjusted for renal function [16].…”

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti‐thymocyte globulin without CMV prophylaxis – a cohort single‐center study

“…In a recent randomized trial, we observed a low incidence of AR (9.4%) and CMV infection (4.7%) in patients receiving 3 mg/kg of rATG induction, low‐dose TAC, and everolimus in KTR receiving no pharmacological prophylaxis for CMV infection [18]. This immunosuppressive regimen, previously with basiliximab and currently with rATG induction, has also been used in low immunological risk KTR [19].…”

Herpesviruses oral shedding and viremia in renal transplant recipients: A longitudinal study

“…All participants received induction therapy to prevent acute rejection consisting of a 500 mg methylprednisolone bolus intraoperatively, and, except for living HLA‐identical kidney transplants, a single 3 mg/kg dose anti‐thymocyte globulin (r‐ATG) within the first 24 hours after graft revascularization. Tacrolimus or cyclosporine, prednisone and either azathioprine, mycophenolate or mTOR inhibitors were all administered from day 1 16 . In the first observation period (15‐20 days), the dose of immunosuppressants was still being adjusted, while in the second period (45‐60 days) the maintenance dose was already established for each patient.…”

“…Preemptive therapy or treatment of CMV disease consisted of intravenous 5 mg/kg b.i.d. ganciclovir, adjusted for renal function 16 …”