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Am J Transplant. 2018 Apr;18(4):907-915. doi: 10.1111/ajt.14504. Epub 2017 Oct 24.

Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation.

Author information

1
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
2
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
3
Department of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
4
Clinimmune Labs, Aurora, CO, USA.

Abstract

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 C0 (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 C0  < 8 ng/mL was associated with dnDSAs by 6 months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32-4.79, P = .005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, P = .004), and there was a graded increase in risk with lower mean TAC C0 . 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 12 months and death-censored graft loss by 5 years (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.

KEYWORDS:

alloantibody; clinical research/practice; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression/immune modulation; kidney (allograft) function/dysfunction; kidney transplantation/nephrology

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