Low-dose cidofovir and conversion to mTOR-based immunosuppression in polyomavirus-associated nephropathy

Transpl Infect Dis. 2020 Apr;22(2):e13228. doi: 10.1111/tid.13228. Epub 2019 Dec 16.

Abstract

Background: Polyomavirus-associated nephropathy (PVAN) remains a relevant complication following kidney transplantation with allograft loss rates of up to 50%. Reduction in overall immunosuppression is a cornerstone of therapy, whereas no specific antiviral regimen has shown conclusive benefit to date. The present case series demonstrates the efficacy of a dual therapeutic approach with low-dose cidofovir and conversion to mTOR-based immunosuppression in PVAN.

Methods: Patients with biopsy-proven PVAN having received low-dose cidofovir (0.25 mg/kg) according to the Tübingen Cidofovir Protocol and been converted to mTOR-based immunosuppression were analyzed retrospectively.

Results: Twenty-three patients with a median follow-up of 2.24 [IQR 1.55-5.01] years were included in the analysis. Median time to PVAN diagnosis was 268 [IQR 153-869] days after transplantation. Polyomavirus clearance from plasma was achieved in 78% of patients after a median of 118 [IQR 76-293] days. Of the 23 patients, nine patients (39%) lost their allograft function during follow-up, but only three of these (13%) due to PVAN. Fourteen patients (61%) stabilized or improved allograft function. The cidofovir protocol allowed for specific antiviral therapy without adverse nephrotoxicity, even in patients with low allograft function.

Conclusions: Low-dose cidofovir and conversion to mTOR-based immunosuppression allow for effective virus clearance and preservation of allograft function in a high proportion of patients with PVAN and progressive allograft dysfunction and may prolong allograft survival in these patients.

Keywords: BKV; cidofovir; mTOR; polyoma; polyomavirus-associated nephropathy; renal transplantation.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Biopsy
  • Cidofovir / administration & dosage
  • Cidofovir / therapeutic use*
  • Humans
  • Immunosuppression Therapy*
  • Kidney / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / virology
  • Kidney Transplantation / adverse effects
  • Male
  • Middle Aged
  • Polyomavirus
  • Polyomavirus Infections / drug therapy*
  • Polyomavirus Infections / immunology
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / immunology*
  • Tumor Virus Infections / drug therapy
  • Tumor Virus Infections / immunology

Substances

  • Antiviral Agents
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Cidofovir