title: Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation.
abstract: OBJECTIVE
  The purpose of this study is to investigate tacrolimus trough-level variability from 3 to 12 months following transplantation and its association with allograft survival in renal transplant recipients.
  
  
  METHODS
  In this observational cohort study, tacrolimus trough-level variability was used as the predictor of all-cause allograft failure (defined as return to dialysis) and patient survival (all-cause mortality).
  
  
  RESULTS
  In total, 394 transplants were included in the analysis. Sixty-two transplants failed during the study. Tacrolimus trough-level variability across quartile groups were: Q1 median variability 12.5 %, range 4.76-15.71 % (n = 99), Q2 median variability 18.17 %, range 15.74-21.29 % (n = 96), Q3 median variability 24.63 % range 21.42-28.88 % (n = 100), Q4 median variability 36.91 %, range 28.91-81.9 % (n = 99). Higher tacrolimus trough-level variability was associated with inferior allograft survival in univariate models [hazard ratio per quartile increase (HR), 1.46, 95 % CI 1.16-1.83, p value = 0.001] and multivariate models (HR 1.36, 95 % CI 1.05-1.78, p value = 0.019). Higher tacrolimus trough-level variability was not associated with patient survival; univariate model (HR 1.25, 95 % CI 0.90-1.74, p value = 0.17), multivariate model (HR 1.25, 95 % CI 0.86-1.83, p value = 0.23).
  
  
  CONCLUSIONS
  Inferior renal allograft survival was observed in recipients with higher variability in tacrolimus trough-levels.
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland. johnaoregan@physicians.ie.
authors.forename: John A
authors.initials: JA
authors.lastname: O'Regan
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Canney
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Dervla M
authors.initials: DM
authors.lastname: Connaughton
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Kelly
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Williams
authors.affiliation: Renal Laboratory, Department of Biochemistry, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Collier
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Declan G
authors.initials: DG
authors.lastname: deFreitas
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
authors.affiliation: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Conlon
mesh_terms: D000328:Adult; D064591:Allografts; D016009:Chi-Square Distribution; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D006435:Renal Dialysis; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Kidney; Tacrolimus; Transplantation; Variability