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

Arturo Blazquez-Navarro,Christian Hugo,Nicole Wittenbrink,Nina Babel,Chris Bauer,Chantip Dang-Heine,Oliver Witzke,Timm H Westhoff,Kerstin Wolk,Robert Sabat,Petra Reinke,Birgit Sawitzki,Michal Or-Guil,Oliver Thomusch

doi:10.3389/fphar.2020.534681

Abstract

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: −11.8 ± 4.3 ml min−1·1.73 m−2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect.

Highlights

Cytomegalovirus (CMV) is a herpesvirus often reported as the most important viral pathogen after kidney transplantation (Elfadawy et al, 2013; Le Page et al, 2013; Fehr et al, 2015)
To assess the effects of CMV prevention strategy on transplantation outcome, we retrospectively analyzed the cohort of an existent study (N 540 patients from 18 centers) with a female ratio of 35.9% (N 194) (Thomusch et al, 2016; Blazquez-Navarro et al, 2018)
Patients were grouped into two sub-cohorts, based on whether they started an antiviral therapy during the first two post-transplant weeks or not

Summary

Introduction

Cytomegalovirus (CMV) is a herpesvirus often reported as the most important viral pathogen after kidney transplantation (Elfadawy et al, 2013; Le Page et al, 2013; Fehr et al, 2015). In the pre-emptive strategy, patients are regularly monitored for CMV through quantitative polymerase chain reaction (qPCR) or pp antigenemia test; (val) ganciclovir is only administered after a positive test, ideally before any symptoms of CMV syndrome or disease manifest (KDIGO Transplant Work Group, 2009; Kotton et al, 2018). The pre-emptive strategy leads to a reduction of unnecessary treatments, which is advantageous with respect to the appearance of side effects and resistances against antiviral drugs (KDIGO Transplant Work Group, 2009; Kotton et al, 2018)

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