Use of Everolimus-based Immunosuppression to Decrease Cytomegalovirus Infection After Kidney Transplant

Exp Clin Transplant. 2016 Aug;14(4):361-6. doi: 10.6002/ect.2015.0292. Epub 2016 Apr 4.

Abstract

Objectives: Cytomegalovirus infection and disease remain an issue in solid-organ transplant. Universal prophylaxis is more cost-effective than a preemptive strategy and is associated with significantly less Cytomegalovirus resistance after kidney transplant, especially in Cytomegalovirus-seropositive donors and Cytomegalovirus-seronegative recipients.

Materials and methods: Registry data and meta-analyses have shown that mammalian target of rapamycin inhibitors (sirolimus- and everolimus-based immunosuppression) are associated with significantly less Cytomegalovirus events in de novo kidney transplant patients than in patients who are treated with calcineurin inhibitors plus mycophenolate-based immunosuppression.

Results: Recent pooled analyses of 3 randomized controlled trials in de novo kidney transplant patients, where immunosuppression was based on cyclosporine with either mycophenolate or everolimus, showed that patients who received everolimus had significantly less Cytomegalovirus events (Cytomegalovirus viremia, Cytomegalovirus infection/disease) than those who received mycophenolate, with or without cytomegalovirus as prophylaxis. An even more recent prospective randomized controlled study on de novo kidney transplant patients with no anticytomegalovirus prophylaxis demonstrated that everolimus-based immunosuppression plus low-dose tacrolimus was associated with significantly less Cytomegalovirus infection than standard-dose tacrolimus plus mycophenolate.

Conclusions: The potential benefits are not fully known of such a therapeutic strategy to limit the long-term indirect effects mediated by Cytomegalovirus infections.

Publication types

  • Review

MeSH terms

  • Cytomegalovirus / immunology*
  • Cytomegalovirus / pathogenicity
  • Drug Therapy, Combination
  • Everolimus / adverse effects
  • Everolimus / therapeutic use*
  • Evidence-Based Medicine
  • Graft Rejection / enzymology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Host-Pathogen Interactions
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / immunology
  • Opportunistic Infections / prevention & control*
  • Opportunistic Infections / virology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Risk Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors
  • Treatment Outcome
  • Virus Activation

Substances

  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases