Antiviral toxicities in pediatric solid organ transplant recipients

Area of Science:

• Pediatric Transplant Medicine
• Virology
• Pharmacology

Background:

• Cytomegalovirus (CMV) infection is a significant risk for pediatric solid organ transplant (SOT) recipients.
• Valganciclovir (VGCV) is a standard prophylactic agent to prevent CMV disease in these vulnerable patients.
• The frequency and contributing factors of VGCV-associated toxicities in pediatric SOT recipients remain incompletely understood.

Purpose of the Study:

• To determine the incidence and risk factors for hematologic and renal toxicities associated with VGCV prophylaxis in pediatric SOT recipients.
• To evaluate the relationship between VGCV exposure and the development of specific adverse events.
• To assess the impact of VGCV dosing on toxicity profiles.

Main Methods:

• Retrospective cohort study of pediatric SOT recipients from January 2012 to June 2018.
• Analysis of hematologic and renal toxicities from day 15 to 1-year post-transplant.
• Utilized marginal rate models to assess the risk of kidney injury and neutropenia in relation to VGCV prophylaxis.

Main Results:

• VGCV prophylaxis was administered on 20.1% of follow-up days across 281 SOT procedures.
• Incidence rates of kidney injury, leukopenia, and neutropenia were significantly elevated during VGCV prophylaxis compared to periods without antiviral use.
• Multivariable analysis revealed VGCV prophylaxis significantly increased the risk of kidney injury (RR 1.79) and neutropenia (RR 4.82).

Conclusions:

• Toxicities, including kidney injury and neutropenia, are common in pediatric SOT recipients receiving VGCV prophylaxis.
• VGCV prophylaxis is independently associated with an increased risk of developing kidney injury and neutropenia.
• VGCV dosing levels did not influence the occurrence of kidney injury or neutropenia, suggesting inherent risks associated with the drug's use.