Katelyn R Richards1, David Hager, Brenda Muth, Brad C Astor, Dixon Kaufman, Arjang Djamali. 1. 1 Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI. 2 Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI. 3 Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI. 4 Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI. 5 Address correspondence to: Katelyn R. Richards, PharmD, BCPS, Department of Pharmacy, University of Wisconsin Hospital and Clinics, 600 Highland Ave, Madison, WI 53792.
Abstract
BACKGROUND: 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.
BACKGROUND: 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±SDtacrolimus 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.
Authors: Gregory L Hundemer; Anand Srivastava; Kirolos A Jacob; Neeraja Krishnasamudram; Salman Ahmed; Emily Boerger; Shreyak Sharma; Kapil K Pokharel; Sameer A Hirji; Marc Pelletier; Kassem Safa; Win Kulvichit; John A Kellum; Leonardo V Riella; David E Leaf Journal: Nephrol Dial Transplant Date: 2021-01-01 Impact factor: 5.992
Authors: David J Taber; Mulugeta G Gebregziabher; Titte R Srinivas; Kenneth D Chavin; Prabhakar K Baliga; Leonard E Egede Journal: Pharmacotherapy Date: 2015-05-23 Impact factor: 4.705
Authors: Jean-Baptiste Woillard; Michel Mourad; Michael Neely; Arnaud Capron; Ron H van Schaik; Teun van Gelder; Nuria Lloberas; Dennis A Hesselink; Pierre Marquet; Vincent Haufroid; Laure Elens Journal: Front Pharmacol Date: 2017-06-08 Impact factor: 5.810