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

Clin Transplant. 2019 Oct;33(10):e13689. doi: 10.1111/ctr.13689. Epub 2019 Oct 8.

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.

Keywords: antibiotic prophylaxis; clinical trial design; cytomegalovirus; infection and infectious agents; mTOR inhibitors.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antilymphocyte Serum / administration & dosage
  • Brazil / epidemiology
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / microbiology
  • Everolimus / administration & dosage
  • Female
  • Follow-Up Studies
  • Graft Rejection / diagnosis
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Incidence
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prednisone / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Tacrolimus / administration & dosage

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Everolimus
  • thymoglobulin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Prednisone
  • Tacrolimus