Methods: All patients at Seattle Children’s Hospital from March 2010 through March 2015 who received cidofovir and had AdV detected from any site were studied. Patients were grouped into two cohorts based on whether acute kidney injury (AKI) was documented during cidofovir therapy. AKI was defined as an increase in serum creatinine (SCr) of ≥ 0.3 mg/dL from baseline, or the requirement for continuous renal replacement therapy (CRRT) or hemodialysis. Mortality data, viral loads, cidofovir dosing, infection with additional viruses, and presence of concomitant nephrotoxic medications were assessed. A standard dose of 1mg/kg three times weekly for cidofovir is generally utilized at our institution. For some patients, particularly those with higher viral loads, 5 mg/kg/week with hyperhydration and probenecid for renal protection, is used instead.
Results: Six patients (6 courses of cidofovir) in the AKI group and 15 patients (17 courses) in the non-AKI group were studied. Baseline SCr and concomitant nephrotoxic medications in both groups were similar. The AKI group had higher viral loads, received higher initial doses of cidofovir, and responded less well clinically, based on slower clearance of virus. All AKI patients expired vs none of the group without renal dysfunction. The average weekly dose of cidofovir in AKI patients was higher than in those who did not develop nephrotoxicity.
Conclusion: Pediatric patients requiring cidofovir for AdV are at serious risk of morbidity and mortality. Severe nephrotoxicity is seen in a significant proportion of these patients, and those patients have poor outcomes. Cidofovir dosing may need to be altered in pediatric patients with renal dysfunction and other alternatives, such as brincidofovir, need to be considered for these patients.
research support to my institution
J. Englund, Chimerix: Investigator , Research support