Long-term outcomes of pre-emptive valganciclovir compared with valacyclovir prophylaxis for prevention of cytomegalovirus in renal transplantation.
Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.
Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, alej Svobody 80, 304 60 Pilsen, Czech Republic. reischig@fnplzen.cz
Tomas
T
Reischig
Petra
P
Hribova
Pavel
P
Jindra
Ondrej
O
Hes
Mirko
M
Bouda
Vladislav
V
Treska
Ondrej
O
Viklicky
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001284:Atrophy; D001706:Biopsy; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006085:Graft Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000473:pathology / Q000821:virology; D016030:Kidney Transplantation / Q000401:mortality; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D000077483:Valacyclovir; D000077562:Valganciclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000998:Antiviral Agents; D000077562:Valganciclovir; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D000212:Acyclovir