Fewer cytomegalovirus complications after kidney transplantation by de novo use of mTOR inhibitors in comparison to mycophenolic acid

Transpl Infect Dis. 2016 Feb;18(1):79-88. doi: 10.1111/tid.12494. Epub 2016 Feb 3.

Abstract

Background: Cytomegalovirus (CMV) is a risk factor for patient and graft survival after kidney transplantation.

Methods: We retrospectively analyzed risk factors for CMV infection in 348 patients who received a kidney transplant donated after brain death (n = 232) or by living donation (n = 116) between 2008 and 2013. Of the 348 patients analyzed, 91 received a mammalian target of rapamycin inhibitor (mTORi)-based immunosuppressive regimen. A total of 266 patients were treated with standard immunosuppression (Group 1) consisting of basiliximab induction, calcineurin inhibitor (CNI), and either mycophenolic acid (MPA, n = 219) or everolimus (EVE) (n = 47). We also included 82 patients who received more intense immunosuppression (Group 2) with lymphocyte depletion, CNI, plus either MPA (n = 38) or EVE (n = 44). Only patients in the high-risk constellation received CMV prophylaxis in Group 1, while all patients in Group 2 received prophylaxis for 6 month.

Results: The overall rate of CMV infections was low with 10.1% in all patients. Despite the different prophylaxis strategies applied, no difference was seen in CMV infections between Group 1 (10.9%) and Group 2 (13.6%). A multivariate analysis revealed that patients on EVE had fewer CMV complications compared with patients on MPA (P = 0.013, odds ratio [OR] 4.8, confidence interval [CI] 1.4-16.5). Donor and recipient age >65 years was an independent risk factor (P = 0.002, OR 3.2, CI 1.5-6.7) for CMV infections. Patients with CMV infections had significantly worse graft function after 2 years (P = 0.001).

Conclusion: CMV is a significant risk factor for long-term graft outcome. Patients treated with EVE developed fewer CMV complications compared to patients on MPA. The use of mTORi is useful in patients at high risk of developing CMV infections.

Keywords: CMV prophylaxis; cytomegalovirus; everolimus; immunosuppression; kidney transplantation; mTOR inhibitors.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Infections / virology
  • Everolimus / therapeutic use*
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Immunosuppressive Agents
  • Everolimus
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid