title: Tacrolimus Trough Levels as a Risk Factor for Acute Rejection in Renal Transplant Patients.
abstract: BACKGROUND
  Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR).
  
  
  METHODS
  This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed.
  
  
  RESULTS
  We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration.
  
  
  CONCLUSIONS
  In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.
authors.affiliation: Department of Transplantation, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Arreola-Guerra
authors.affiliation: Department of Nephrology-Mineral Metabolism, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
authors.forename: Marcos
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Department of Nephrology-Mineral Metabolism, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morales-Buenrostro
authors.affiliation: Department of Transplantation, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Vilatobá
authors.affiliation: Department of Transplantation, National Institute of Medical Science and Nutrition, Salvador Zubirán, Mexico City, Mexico.
authors.forename: Josefina
authors.initials: J
authors.lastname: Alberú
mesh_terms: D000208:Acute Disease; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus