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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(s) -
Davis Scott,
Gralla Jane,
Klem Patrick,
Tong Suhong,
Wedermyer Gina,
Freed Brian,
Wiseman Alexander,
Cooper James E.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14504
Subject(s) - medicine , tacrolimus , hazard ratio , odds ratio , confidence interval , kidney transplantation , transplantation , trough level , adverse effect , calcineurin , cohort , urology , gastroenterology
De novo donor‐specific antibodies (dn DSAs ) 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 dn DSA s has not been established. We evaluated mean TAC C 0 (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dn DSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C 0 < 8 ng/mL was associated with dn DSAs 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 C 0 . TAC time in the therapeutic range of <60% was associated with dn DSA s ( 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 dn DSA s, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.