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Kidney Week

Abstract: FR-PO869

Impact of Antiviral Dose Adjustments on Risk for Breakthrough CMV Viremia After Kidney Transplantation

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Bunnapradist, Suphamai, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Phonphok, Korntip, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Spanuchart, Ittikorn, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Duong, Tin N., David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Lum, Erik Lawrence, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Reed, Elaine F., David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Schaenman, Joanna, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
Background

CMV infection continues to cause significant morbidity in kidney transplant recipients in the modern era of transplantation. CMV seronegative patients with CMV seropositive donors are at highest risk for complications, including invasive disease and loss of allograft function. Inadequate drug dosing is associated with breakthrough viremia and drug resistance. We sought to evaluate whether drug dosing was associated with CMV viremia.

Methods

We reviewed CMV PCR testing results from 1297 adult kidney transplant recipients (excluding multiorgan transplants) between the years 2013-2017. We performed chart review to obtain antiviral prophylaxis regimens prior to viremia, and assessed sCr and calculated GFR at regimen start. Adequacy of dose adjustment for renal insufficiency was determined based on the package insert for valganciclovir to determine whether there was an association between antiviral dosing and breakthrough CMV viremia.

Results

We identified 14 seronegative kidney transplant recipients who developed CMV viremia during the first year after transplantation. 9 had received basiliximab (64%) and 5 (36%) antithymocyte globulin. 3 patients experienced biopsy-proven rejection (2 ACR and 1 AMR) prior to CMV viremia. The median time to viremia was 75 days (range 62-178). 5 patients (36%) were not taking valganciclovir at the time of viremia detection, while 9 patients (64%) were on valganciclovir. 8 of the 9 (89%) patients on valganciclovir were on dose-adjusted regimens at the time of viremia, correct according to the Valcyte package insert, at doses ranging from 450 mg once daily to 450 mg 3x/week.

Conclusion

Despite appropriate valganciclovir dose-adjustment, breakthrough CMV viremia occurred. This suggests that renal impairment is associated with CMV infection either because standard dose adjustments are inadequate, impaired drug absorption, or exacerbation of impaired CMV immune response. This suggests a role for therapeutic drug monitoring, and for the need for more effective antiviral prophylaxis medications. Future studies will evaluate patterns of drug dosing associated with CMV viremia in seropositive transplant recipients. Immunologic analysis will be performed to identify patients lacking effective CMV-specific immune response in need of prolonged antiviral prophaylaxis.