A Real-World Clinical Evaluation of Ganciclovir Exposure and Cytomegalovirus Viremia Outcomes After Adult Kidney Transplantation
Lukas K. van Vugt, Rawan Saleh, Dennis A. Hesselink, Brenda C. M. de WinterBackground:
The efficacy and toxicity of valganciclovir prophylaxis are determined by ganciclovir (GCV) exposure. As GCV is predominantly eliminated through glomerular filtration, kidney transplant recipients are at risk of both under- and overexposure. Kidney function is dynamic and GCV exposure may be off-target shortly after kidney transplantation and in kidney transplant recipients with delayed graft function (DGF). However, the extent of GCV under- and overexposure in the early phase after kidney transplantation has not been well described.
Methods:
This was a retrospective, single-center analysis of adult patients who received valganciclovir prophylaxis and underwent at least one predose steady-state GCV concentration measurement during the first month after kidney transplantation. Data on GCV measurements, target attainment, and clinical outcomes, including cytomegalovirus (CMV) viremia and leukopenia, were collected and analyzed.
Results:
Overall, 353 patients were included, with 357 predose and steady-state GCV concentration measurements. GCV exposure was highly variable early after kidney transplantation, especially in patients with poorly functioning grafts and those undergoing dialysis. Overall, there was a large proportion of patients with GCV exposure below the target, especially those with higher estimated kidney function, despite many receiving high GCV dosages. However, despite the frequent occurrence of off-target GCV exposure, no association was observed between DGF, GCV exposure, and CMV viremia.
Conclusions:
In the early phase after kidney transplantation, exposure to GCV is highly variable among patients and underexposure to GCV occurs frequently. However, DGF was not associated with reduced exposure to GCV or CMV viremia, nor was early exposure to GCV correlated with CMV outcomes or leukopenia.