title: Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial.
abstract: BACKGROUND
  Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.
  
  
  METHODS
  Prophylaxis was 2 × 450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2 × 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy).
  
  
  RESULTS
  Overall, CMV infection (asymptomatic CMV viral load ≥ 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P>0.05). Tolerability was similar for both treatment groups.
  
  
  CONCLUSIONS
  Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.
authors.affiliation: Department of Nephrology, University Duisburg-Essen, Essen, Germany. oliver.witzke@uk-essen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Hauser
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolters
authors.forename: Martin
authors.initials: M
authors.lastname: Nitschke
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001317:Austria; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005858:Germany; D006084:Graft Rejection / Q000503:physiopathology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D014180:Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir