A Systematic Review and Meta-analysis of Prophylactic versus Pre-emptive Strategies for Preventing Cytomegalovirus Infection in Renal Transplant Recipients

BACKGROUND In kidney transplant (KT) recipients, CMV infection poses significant morbidity and mortality. Both prophylactic and pre-emptive approaches for preventing CMV infection have been utilized. OBJECTIVE To compare the effectiveness of routine prophylaxis vs. pre-emptive treatment for preventing CMV disease after KT. METHODS We conducted a systematic review and meta-analysis comparing the effectiveness of routine prophylaxis vs. pre-emptive treatment for preventing CMV disease after KT. Combining 4 comprehensive search terms (CMV, renal transplant, prophylaxis, pre-emptive); we searched PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through January 2011. We also evaluated studies referenced in review articles and abstracts from meetings of major nephrology and transplant societies (2009-2011). Two authors independently extracted data and assessed methodological criteria. The primary outcome was the pooled estimate of the odds ratio (OR) of developing CMV infection. Secondary outcomes included OR of acute rejection, OR of graft loss and OR of death within first year of KT. Comprehensive Meta-analysis V2 software was used for data analysis. RESULTS Analysis of 9 randomized controlled trials (991 patients; ganciclovir=5, valganciclovir=4) with CMV infection as an outcome revealed the OR of CMV infection to be 0.34 (95% CI: 0.25-0.46, p=0.008) for the prophylactic vs. the pre-emptive groups. The OR of acute rejection (7 studies; 1358 patients) was 0.52 (95% CI: 0.41-0.67, p=0.001) with prophylactic approach compared to pre-emptive treatment; graft loss (7 studies; OR 0.52 [95% CI: 0.34-1.12, p=0.32] and mortality (6 studies; OR 0.84 [95% CI: 0.62-1.23, p=0.23]) were similar between the two groups. CONCLUSIONS Prophylactic approach is superior to pre-emptive approach in preventing CMV infection within the first year of kidney transplant. The risk of developing acute rejection is also lower with prophylactic approach in the first year of transplant but there is no significant difference in graft loss or mortality with either approach.