Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parallel group, open-label, randomized controlled trial

Abstract

BackgroundCytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft.MethodsFrom November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population.ResultsAmong the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11–0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years.ConclusionsValganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12610000016033). Registered on September 26, 2007Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3493-y) contains supplementary material, which is available to authorized users.

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

“…23,24 Regarding BKV, the observed pattern is in line with three recent studies. [46][47][48] On the other hand, we did not observe any effect of prevention strategy on EBV (re)activation. 49 This is relevant, as there is currently no consensus in the literature on this topic.…”

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

“…While we have already reported a negative effect of prophylaxis on rejection within the VIPP study–albeit only for the D − R + subgroup–this study would be the first to suggest such an association in the entire cohort ( Witzke et al, 2012 ; Witzke et al, 2018 ). Regarding BKV, the observed pattern is in line with three recent studies ( Reischig et al, 2015 ; Reischig et al, 2018 ; Reischig et al, 2019 ). This effect could be explained through the increased incidence of acute rejection among patients in the prophylactic strategy group, as episodes of acute rejection and anti-rejection treatment have been associated with BKV reactivation ( Schold et al, 2009 ; Borni-Duval et al, 2013 ).…”

BK polyomavirus and valganciclovir: Highly suspected association urgently calling for a new randomized trial

“…In our cohort, the association of (full dose) valganciclovir prophylaxis with increased risk of BKV viremia and PVAN seems highly probable. Despite the limited sample size, the difference (42% vs 26%, P = .046 by log rank test) was apparent even in a separate 3‐year analysis of valganciclovir‐versus‐valacyclovir study . Notwithstanding, evaluation of valganciclovir prophylaxis deserves a complex view because of the low number of PVAN or persistent BKV viremia events that triggered progression of graft fibrosis and renal function decline .…”

“…Notwithstanding, evaluation of valganciclovir prophylaxis deserves a complex view because of the low number of PVAN or persistent BKV viremia events that triggered progression of graft fibrosis and renal function decline . Effective prevention of CMV by valganciclovir and possible suppression of T‐cell proliferation may be associated with less acute rejection and even graft fibrosis . There is a strong need for randomized studies comparing valganciclovir with preemptive therapy or nonvalganciclovir prophylaxis including CMV‐ and BKV‐specific immunity measurements.…”