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Abstract: FR-PO902

Safety and Efficacy of Management of Refractory Cytomegalovirus Infection in Kidney Transplant Recipients Treated with Foscarnet and Conversion from Antimetabolite to mTOR Inhibitor

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Foresto, Renato Demarchi, Federal University of São Paulo, São Paulo, Brazil
  • Hazin, Maria Amelia, UNIFESP, São Paulo, Brazil
  • Zapata, Alejandro, UNIFESP, São Paulo, Brazil
  • Santos, Daniel wagner Castro lima, Federal University of Sao Paulo, Sao Paulo, Brazil
Background

Cytomegalovirus (CMV) infection is a frequent complication after kidney transplantation and it is associated with graft dysfunction and increased mortality. Foscarnet may be an alternative to ganciclovir-resistant or CMV refractory infections. As additional therapies, there are limited published studies assessing the conversion from antimetabolite (mycophenolate or azathioprine) to mTOR inhibitor (mTORi) to avoid recurrence.

Methods

We retrospectively evaluated the adverse events and outcomes of the treatment of refractory CMV with foscarnet from January 1, 2010 to April 30, 2018 and we analyze the outcomes of the group of patients who were submitted to conversion from antimetabolite to mTORi.

Results

We evaluated 28 patients with refractory CMV treated with foscarnet; 89.3% received thymoglobulin as induction therapy and, as a maintenance therapy, 46.4% started with azathioprine and 53.6% with mycophenolate. The first episode of CMV occurred, on average, 40 days after transplantation. The average duration of therapy with ganciclovir was 98 days and 34.9 days with foscarnet. The UL97 mutation was present in all cases and the UL54 mutation was in 28.7%. After treatment with foscarnet, 17.8% had CMV recurrence. During treatment, 92.8% had antimetabolite discontinued, 64.3% were converted to mTORi. There were 19 recurring cases of CMV, 7 of them (36.8%) after conversion to mTORi against 12 cases (63.2%) in patients that not received mTORi. About the adverse effects to foscarnet, hypomagnesemia is the most common (82.1%), followed by hypophosphatemia (57.1%) and leucopenia (46.4%). There were 4 graft rejections and 3 deaths.

Conclusion

Prolonged use of ganciclovir with doses not adjusted for renal function as well as the immunological status of the transplanted patient are considered the main risk factors for resistance to ganciclovir therapy. Foscarnet seems to be an effective alternative in the control of viremia and treatment of CMV invasive disease. However, adverse events should be monitored cautiously, avoiding unfavorable outcomes for the graft. Preliminary data show that the conversion from antimetabolite to mTOR inhibitor is effective to avoid recurrence of CMV episodes.