A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients
Abstract
Background The optimal regimen for the prevention of cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in terms of reducing indirect CMV effects, has not been defined.
Methods This was an open-label, single-center, randomized clinical trial of valganciclovir prophylaxis vs preemptive therapy in 140 kidney transplant recipients recruited between June 2013 and May 2018. CMV-seronegative recipients with negative donors (D-R-) were excluded. Patients were randomized 1:1 to receive either valganciclovir prophylaxis, 900 mg, daily for 3 months (6 months in D+R-) (n=70) or preemptive therapy (valganciclovir, 900 mg, twice daily until 2 consecutive negative tests) for CMV DNAemia (>=1000 IU/mL) detected by weekly CMV PCR for 4 months (n=70). The primary outcome was the incidence of acute rejection at 12 months, as confirmed by biopsy. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia.
Results The incidence of acute rejection was numerically lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 vs 23%, 16/70, P=0.112 [HR, 0.52, 95% CI, 0.23-1.19]). Subclinical rejection at 3 months was lower in the prophylaxis group (13% vs 29%, P=0.027). Both regimens prevented CMV disease (4% vs 4%, P=0.974). Preemptive therapy resulted in higher rates of CMV DNAemia (44% vs 75%, P=2000 IU/mL, P<0.001) but lower valganciclovir exposure (P<0.001) and neutropenia (P=0.019).
Conclusion Among kidney transplant recipients, the use of valganciclovir prophylaxis, compared with preemptive therapy, did not result in a significantly lower incidence of acute rejection.