Nephrotoxicity of Intravenous Ganciclovir in Pediatric Hematopoietic Cell Transplant Recipients

Abstract

Background: Associations between ganciclovir and severe nephrotoxicity are incompletely defined. Studies incorporating the time-varying nature of medication exposures and those that address confounding by indication are particularly scarce in children undergoing hematopoietic cell transplantation. Methods: We identified children undergoing hematopoietic cell transplantation in the Pediatric Health Information System database and tracked them for 1 year following transplantation. The primary exposure of interest was the use of ganciclovir, which was treated as a time-varying variable. Secondary exposures of interest included cidofovir, foscarnet, amphotericin B, aminoglycosides, vancomycin and calcineurin inhibitors. The primary outcome of interest was renal replacement therapy, which was assessed using marginal structural Cox proportional hazards regression model incorporating time-varying variables and inverse-probability-of-treatment weight. Results: Of 17,924 children who underwent hematopoietic cell transplantation during the study period, 3078 (17.2%) had exposure to ganciclovir. In marginal structural Cox proportional hazards regression model incorporating time-varying variables and inverse-probability-of-treatment weight, ganciclovir was associated with an increased hazard of renal replacement therapy (adjusted hazard ratio: 1.84, 95% confidence interval: 1.22–2.76). Some of secondary exposures of interest, including cidofovir, amphotericin B and vancomycin, also were associated with renal replacement therapy. Conclusions: Intravenously administered ganciclovir is associated with renal dysfunction severe enough to require renal replacement therapy in pediatric hematopoietic cell transplant recipients. Ganciclovir should be used with caution and close monitoring. Approaches to mitigate the risks of nephrotoxicity should be investigated.