title: Risk factors for BK virus infection in the era of therapeutic drug monitoring.
abstract: BACKGROUND
  Overimmunosuppression is a widely recognized risk factor for BK virus (BKV) infection, particularly with the combination of tacrolimus, mycophenolate mofetil (MMF), and steroids. Nevertheless, the exact impact of exposure to tacrolimus and MMF is not well understood.
  
  
  METHODS
  We examined 240 kidney recipients between 2006 and 2008. BKV was monitored every 2 months in the urine or blood. A kidney biopsy was performed when viremia exceeded 10 copies/mL.
  
  
  RESULTS
  Ninety-five (40%) patients had sustained viruria, 48 (20%) sustained viremia, and 17 (7%) biopsy-proven polyomavirus-associated nephropathy. The mean time-to-occurrence was 7.6, 7.9, and 9.7 months for viruria, viremia, and polyomavirus-associated nephropathy. Risk factors associated with BKV infection in univariate analyses were retransplantation, panel-reactive antibody more than 0%, cytomegalovirus D+/R-, cold ischemia time, delayed graft function, induction with antithymocyte globulins, acute rejection before month 3 (M3), tacrolimus trough levels more than 10 ng/mL, and M3 AUC0-12 hr more than 50 hr mg/L. Multivariate analyses showed that cytomegalovirus D+/R- (adjusted hazard ratio [AHR], 2.03; P=0.05), acute rejection (AHR, 5.4; P<0.001), and mycophenolic acid AUC0-12 hr more than 50 hr mg/L (AHR, 3.6; P=0.001) were risk factors for BKV.
  
  
  CONCLUSIONS
  This study identified a link between a state of increased immunosuppression and BKV infection, especially in patients with higher MMF exposure and elevated tacrolimus trough levels at M3.
authors.affiliation: Nephrology-Transplantation Department, University Hospital, Strasbourg, France. claire.borniduval@chru-strasbourg.fr
authors.forename: Claire
authors.initials: C
authors.lastname: Borni-Duval
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Olagne
authors.forename: Peggy
authors.initials: P
authors.lastname: Perrin
authors.forename: Laura
authors.initials: L
authors.lastname: Braun-Parvez
authors.forename: Françoise
authors.initials: F
authors.lastname: Heibel
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001739:BK Virus / Q000302:isolation & purification*; D001706:Biopsy; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D027601:Polyomavirus Infections / Q000175:diagnosis*; D051437:Renal Insufficiency / Q000150:complications / Q000628:therapy*; D012307:Risk Factors; D013256:Steroids / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D014766:Viremia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D009173:Mycophenolic Acid; D016559:Tacrolimus