Rationalising Cmv Prophylaxis Post Renal Transplantation

Abstract

Background: Anti-viral prophylaxis strategies with ganciclovir/valganciclovir, adopted based on CMV donor(D) and recipient(R) serostatus, have influenced Cytomegalovirus(CMV) infections post-renal transplant. Current guidelines recommend universal CMV prophylaxis for at least 3 months for all RTX except D−/R− patients. Methods: 97 renal transplant recipients (RTX; Mean age 45.6 years, 46% Male, 61% Chinese) undergoing transplant from January 2006-December 2010 were retrospectively reviewed. CMV viremia was diagnosed for CMV DNA>2,000 copies/mL. Clinical characteristics, immunosuppression and efficacy of anti-viral prophylaxis in preventing CMV viremia were evaluated for RTX stratified by CMV serostatus and ALAb use (Very High:D+R-, High:R+ receiving Thymoglobulin, Moderate:R+ receiving Simulect or no ALAb and Low:D-R-). Duration of prophylaxis was at least 3 months for Very High and High-risk RTX, at least 1 month for Moderate-risk and none for Low- risk RTX. Results: Overall, CMV infections occurred in 30.9% at median interval of 4 months post-transplant and there was no CMV disease on follow up at 1 year. Only Thymoglobulin, but not CMV serostatus was a risk factor for CMV infection on multivariate analysis(P=0.001). Among 37 RTX receiving Thymoglobulin, there was an increased risk for CMV infection if accumulated Thymoglobulin dose exceeded 6mg/kg (14% vs. 56%, < 6 vs. >6mg/kg respectively; p=0.045). 56.7% of CMV infections occurred between the 3rd and 6th month post-transplant. Among 86 RTX at High/Moderate risk for CMV, 37(38.1%) and 39(40.2%) had received Thymoglobulin or Simulect respectively, while 21(21.7%) had not received ALAb. In this cohort, CMV infection occurred in 51.5% of RTX receiving Thymoglobulin at a median interval of 4 months and was not mitigated by type or duration of prophylaxis or anti-metabolite used(p=0.001). Incidence of CMV infection among Moderate risk RTX receiving Simulect or no ALAb were 13.9% and 23.5% respectively; infections were not mitigated by type or duration of prophylaxis. Conclusions: These results suggest that Thymoglobulin is the most important risk factor for CMV infection. Furthermore, as risk for CMV infection is not mitigated by 3 months antiviral prophylaxis in RTX receiving>6mg/kg Thymoglobulin, longer duration of prophylaxis may be needed in this cohort. Contrariwise, risk for CMV infection was low among Moderate-risk RTX receiving Simulect; either 1 month prophylaxis or a pre-emptive approach may be adequate in this cohort. Thus, a selective strategy taking into account type and dose of induction therapy, in addition to CMV serostatus provides a rational approach to preventing CMV infection post renal-transplant.