Low-Dose Valganciclovir Prophylaxis Is Safe and Cost-Saving in CMV-Seropositive Kidney Transplant Recipients

Abstract

Introduction: Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia. Our institution adopted low-dose valganciclovir prophylaxis for intermediate-risk (seropositive) kidney transplant recipients in January 2018. Research Question: To analyze the efficacy (CMV DNAemia), safety (BK virus DNAemia, neutropenia, graft loss, and death), and cost savings associated with this change. Design: We retrospectively compared the above outcomes between CMV-seropositive kidney transplant recipients who received low-dose and standard-dose valganciclovir, transplanted within our institution, between 1/19/2014 and 7/15/2019, using propensity score-adjusted competing risk analyses. We also compared cost estimates between the two dosing regimens, for 3 months of prophylaxis, and for different percentage of patient-weeks with normal renal function, using the current average wholesale price of valganciclovir. Results: We studied 179 CMV-seropositive kidney transplant recipients, of whom 55 received low-dose and 124 standard-dose valganciclovir. The majority received nonlymphocyte depleting induction (basiliximab). Low-dose valganciclovir was at least as effective and safe as, and more cost-saving than standard-dose valganciclovir. Conclusion: This single-center study contributes to mounting evidence for future guidelines to be adjusted in favor of low-dose valganciclovir prophylaxis in CMV-seropositive kidney transplant recipients.

Pitfalls in Valganciclovir Prophylaxis Dose Adjustment Based on Renal Function in Kidney Transplant Recipients

“…Dose adjustments have been proposed to ascertain efficacy, while limiting the potential toxicities associated with higher VCG concentrations, namely, its effect on the bone marrow and associated cytopenias. A lower VGC dosing (450 mg daily for an eGFR ≥60 mL/min/m 2 ) has been shown to significantly reduce the incidence of leucopenia and to be cost-effective [ 21 , 22 ]. For this study, we followed the proposed dose adjustments as shown in the Compendium ® , an open-access Swiss medication database operated by HCI Solutions SA and regularly updated, which provides short monographs, clear clinical decision support and interaction profiles, and dose adjustments based on renal function of the drugs [ 23 ].…”

Therapeutic Myths in Solid Organ Transplantation Infectious Diseases

“…However, ganciclovir-resistant CMV was observed in the reduced-dose group (2 vs 0 patients) [ 34 ]. A study comparing valganciclovir 450 mg daily to 900 mg daily in 179 intermediate-risk KTRs found no difference in rates of CMV reactivation (0% vs 3.4%, respectively, P = .179) or neutropenia [ 35 ]. A study of 90 high-risk SOT recipients observed a lower incidence of leukopenia with reduced-dose valganciclovir (44% vs 75%, P < .01), but with a numerically higher rate of CMV breakthrough infection (13.3% vs 2.2%, P = .11) [ 36 ].…”