Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics |
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Authors: | Ajay K Israni Samy M Riad Robert Leduc William S Oetting Weihua Guan David Schladt Arthur J Matas Pamala A Jacobson DeKAF Genomics Investigators |
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Institution: | 1. Nephrology Division, Department of Medicine, Hennepin County Medical Center, University of Minnesota, , Minneapolis, MN, USA;2. Department of Epidemiology & Community Health, University of Minnesota, , Minneapolis, MN, USA;3. Division of Nephrology, Department of Medicine, University of Minnesota, , Minneapolis, MN, USA;4. Division of Biostatistics, University of Minnesota, , Minneapolis, MN, USA;5. Department of Experimental and Clinical Pharmacology, University of Minnesota, , Minneapolis, MN, USA;6. Department of Surgery, University of Minnesota, , Minneapolis, MN, USA |
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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. |
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Keywords: | acute rejection kidney transplant tacrolimus reduction trough levels |
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