Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics.
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.
['Israni|Ajay K|AK|', 'Riad|Samy M|SM|', 'Leduc|Robert|R|', 'Oetting|William S|WS|', 'Guan|Weihua|W|', 'Schladt|David|D|', 'Matas|Arthur J|AJ|', 'Jacobson|Pamala A|PA|', '|||']
D000328:Adult D000367:Age Factors D065095:Calcineurin Inhibitors D002986:Clinical Trials as Topic D015331:Cohort Studies D005260:Female D006084:Graft Rejection D006801:Humans D007165:Immunosuppression Therapy D007166:Immunosuppressive Agents D016030:Kidney Transplantation D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D016035:Pancreas Transplantation D016016:Proportional Hazards Models D011446:Prospective Studies D051437:Renal Insufficiency D015203:Reproducibility of Results D012307:Risk Factors D016559:Tacrolimus
trough levels acute rejection kidney transplant tacrolimus reduction