Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 18, Issue 4, Pages 907-915Publisher
WILEY
DOI: 10.1111/ajt.14504
Keywords
alloantibody; clinical research; practice; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression; immune modulation; kidney (allograft) function; dysfunction; kidney transplantation; nephrology
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Funding
- National Institutes of Health/National Center for Advancing Translational Sciences Colorado Clinical Translational Science Awards [UL1 TR001082]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001082] Funding Source: NIH RePORTER
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De novo donor-specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common among immunosuppressive approaches used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not been established. We evaluated mean TAC C-0 (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dnDSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C-0<8ng/mL was associated with dnDSAs by 6months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32-4.79, P=.005) and by 12months (OR 2.32, 95% CI 1.30-4.15, P=.004), and there was a graded increase in risk with lower mean TAC C-0. TAC time in the therapeutic range of <60% was associated with dnDSAs (OR 2.05, 95% CI 1.28-3.30, P=.003) and acute rejection (hazard ratio [HR] 4.18, 95% CI 2.31-7.58, P<.001) by 12months and death-censored graft loss by 5years (HR 3.12, 95% CI 1.53-6.37, P=.002). TAC minimization may come at a cost of higher rates of dnDSAs, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes. Minimizing tacrolimus exposure may increase the risk of de novo donor-specific antibodies, and calculating the time tacrolimus is in therapeutic range may be a useful method to identify patients at risk for adverse clinical outcomes.
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