Mitochondrial changes in cidofovir therapy for BK virus nephropathy.
Polyoma (BK) virus nephropathy (BKVN) is often treated with the nucleotide analog cidofovir. An adverse effect of this drug class is proximal tubular toxicity, and ultrastructural abnormalities in proximal tubular mitochondria have been observed in patients treated with similar drugs for other viral infections. We report similar changes in biopsies from BKVN treated with cidofovir. Renal allograft biopsies showing BKVN, on which electron microscopy was performed, were categorized into 3 groups: initial diagnosis (BD), postcidofovir treatment (CT), and posttreatment with immunosuppression reduction (IR). Nineteen cases from each group were randomly selected. Mitochondrial changes were present in 6 biopsies from patients receiving CT therapy (31.5%), ranging from diffuse mitochondrial swelling to profound morphologic changes. No similar abnormalities were seen in other groups. In those with atypical mitochondria, the mean number of cidofovir doses was 2.67, with an average interval between last dose and biopsy of 2.17 weeks. CT patients without mitochondrial changes had a mean of 4.6 doses and an average interval between last dose and biopsy of 27.2 weeks. Some renal transplant patients treated with cidofovir display alterations in proximal tubular mitochondria akin to those seen with similar drugs. The findings support the mitochondrial toxicity of nucleotide analogs.
Talmon
G
G
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. gtalmon@unmc.edu
Cornell
L D
LD
Lager
D J
DJ
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001739:BK Virus; D001706:Biopsy; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D063065:Organophosphonates / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000188:drug therapy* / Q000473:pathology
D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir