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

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.

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large, multi‐centre study

“…According to the study protocol, patients with D+/R‐ mismatch for either CMV or EBV as well as all patients with rATG induction, received a valganciclovir (VGCV) prophylaxis [11]. VGCV prophylaxis was defined as VGCV treatment initiated during the first 14 days, as explained before [12]. Reported MMF dose and tacrolimus trough levels correspond to this same 14 day threshold.…”

Early prediction of renal graft function: Analysis of a multi-centre, multi-level data set

“…Furthermore, based on their risk constellation patients received an anti-cytomegalovirus prophylaxis consisting of valganciclovir. [29]…”

Early prediction of renal graft function: Analysis of a multi-center, multi-level data set

“…Gene expression markers were selected based on their role in operational tolerance or rejection and measured employing TaqMan Gene Expression Assays (Thermo Fisher Scientific). [25][26][27][28] Serum antibodies (SAB) were screened employing HLA-1 mixed antigen bead assay; the raw mean fluorescence intensity for each bead was employed for prediction. [10] The urinary metabolomics spectrum was determined employing nuclear magnetic resonance (NMR), which was binned and normalized to facilitate the analysis.…”

“…The markers used here were already identified as useful in previous studies addressing immunological risk factors of acute transplant rejection. [22][23][24][25][26][27][28] The analysis was performed according to the following strategy: First, predictive models of eGFR-1y were calculated for each marker subset and visit. Second, predictive models were combined to provide a final prediction of eGFR-1y.…”