Mitochondrial changes in cidofovir therapy for BK virus nephropathy

Area of Science:

• Nephrology
• Virology
• Toxicology

Background:

• Polyoma (BK) virus nephropathy (BKVN) is a significant complication in renal transplant recipients.
• Cidofovir, a nucleotide analog, is a common treatment for BKVN.
• Proximal tubular toxicity, including mitochondrial abnormalities, is a known adverse effect of nucleotide analogs.

Purpose of the Study:

• To investigate ultrastructural mitochondrial changes in proximal tubular cells of renal allograft biopsies from BKVN patients treated with cidofovir.
• To compare mitochondrial morphology in biopsies before and after cidofovir treatment.

Main Methods:

• Retrospective analysis of renal allograft biopsies.
• Categorization of biopsies into: initial diagnosis (BD), post-cidofovir treatment (CT), and post-immunosuppression reduction (IR).
• Electron microscopy was used to assess ultrastructural mitochondrial changes in 19 cases per group.

Main Results:

• Mitochondrial abnormalities were observed in 31.5% of biopsies from patients receiving cidofovir treatment (CT group).
• Observed changes ranged from diffuse swelling to profound morphologic alterations.
• No similar mitochondrial abnormalities were detected in the initial diagnosis (BD) or immunosuppression reduction (IR) groups.

Conclusions:

• Cidofovir treatment in BKVN patients is associated with proximal tubular mitochondrial alterations.
• These findings support the hypothesis of mitochondrial toxicity induced by nucleotide analog drugs.
• The study underscores the importance of monitoring for cidofovir-related nephrotoxicity.