Goal tacrolimus concentrations for the prevention of rejection in sensitized renal transplant recipients are not well established.Methods
We evaluated the association between discharge tacrolimus trough concentration and the incidence of biopsy-proven acute rejection (BPAR) in 216 moderately sensitized renal transplant recipients (negative flow crossmatch and positive donor-specific antibodies) treated with tacrolimus.Results
At transplant, the mean±standard deviation (SD) peak panel-reactive antibody was 60±33 and median donor-specific antibody level was a mean fluorescence intensity of 710 (interquartile range, 328–1202). The mean±SD tacrolimus trough concentration at discharge (median postoperative day, 5; interquartile range, 4–7) was 7.6±3.7 ng/dL. Patients were divided into two groups based on a discharge tacrolimus trough concentration of 8 ng/mL. Baseline characteristics were similar between groups. Thirty-four (28.6%) of the 119 patients with a tacrolimus trough concentration less than 8 ng/mL and 19 (19.6%) of 97 patients with concentrations of 8 ng/mL or greater experienced BPAR during a median follow-up of 14±4.7 months (P=0.04). Adjusting for age, race, donor status, and peak panel-reactive antibody, a discharge tacrolimus trough concentration less than 8 ng/mL was significantly associated with a higher risk of BPAR (hazard ratio, 1.84; 95% confidence interval, 1.04–3.25; P=0.04). Serum creatinine, cytomegalovirus, BK viremia, or BK nephropathy at 1 year did not differ between groups.Conclusions
In a patient population predisposed to BPAR, discharge tacrolimus trough concentration less than 8 ng/mL was associated with a nearly two times greater risk of BPAR.