title: Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation.
abstract: BACKGROUND
  The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation.
  
  
  METHODS
  144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R-), use of induction therapy with antithymocyte globulin, treatment of rejection) received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months.
  
  
  RESULTS
  The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R-, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG), 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC=0.849±0.042, p<0.001). Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation.
  
  
  CONCLUSIONS
  Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in preventing severe clinical presentation, including tissue invasive and late cytomegalovirus infection. This strategy is associated with direct and indirect cost-savings.
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: Cahue
authors.initials: C
authors.lastname: Henrique Pinto
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil. Electronic address: heliotedesco@medfarm.com.br.
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosso Felipe
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicolau Ferreira
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Cristelli
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: Laila
authors.initials: L
authors.lastname: Almeida Viana
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Serviço de Urologia, São Paulo, SP, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Aguiar
authors.affiliation: Universidade Federal de São Paulo (Unifesp), Hospital do Rim, Disciplina de nefrologia, São Paulo, SP, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Medina-Pestana
mesh_terms: D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D011292:Premedication; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Cytomegalovirus; Kidney; Preemptive therapy; Transplant