title: Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics.
abstract: Most calcineurin inhibitor (CNI)-based protocols reduce blood trough goals approximately 2-3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model, we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. A total of 1930 patients received TAC-based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time-varying multivariate model, each 1 ng/ml decrease in TAC trough levels was associated with a 7.2% increased risk of AR [hazards ratio (HR) = 1.07, 95% confidence interval (CI) (1.01, 1.14) P = 0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/ml decrease in the TAC trough levels in months 3-6 [HR = 1.23, 95% CI (1.06, 1.43) P = 0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3 and 6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual's risk factors.
authors.affiliation: Nephrology Division, Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA; Department of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Israni
authors.forename: Samy M
authors.initials: SM
authors.lastname: Riad
authors.forename: Robert
authors.initials: R
authors.lastname: Leduc
authors.forename: William S
authors.initials: WS
authors.lastname: Oetting
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.forename: David
authors.initials: D
authors.lastname: Schladt
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Matas
authors.forename: Pamala A
authors.initials: PA
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D000367:Age Factors; D065095:Calcineurin Inhibitors; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016035:Pancreas Transplantation / Q000379:methods; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood* / Q000628:therapy*; D015203:Reproducibility of Results; D012307:Risk Factors; D016559:Tacrolimus / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: acute rejection; kidney transplant; tacrolimus reduction; trough levels