Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: Recent studies suggest that increased tacrolimus (TAC) exposure may help prevent production of donor specific HLA antibodies (DSAs) that mediate chronic rejection of renal transplants. To improve and regularize exposure, we reinforce empty stomach TAC dosing and routinely measure peak levels at 1 ½ hours post-dose. We target peak levels of 20-30 ng/ml and do not taper in low risk or stable patients. This protocol results in more constant, higher TAC exposures than 12 hour level (trough) monitoring without specific attention to food avoidance.
Methods: We retrospectively evaluated this dosing protocol with respect to graft function, donor specific antibody (DSA) formation, viral infection, and TAC pharmacokinetics
Results: 152 consecutive patients were 49.9±13.2 years old; 94% were on triple immunosuppression. Serum creatinine values were stable over the first 3 post transplant years (1.4±0.5 vs 1.7±1.6 mg/dl). 2% developed DSAs that were often measured repeatedly in problematic patients. BK viremia produced no graft losses, and after 1 year, occurred de novo in 1-2% of patients, with median titer < 10,000 copies/ml. 1 patient developed inconsequential CMV viremia. Serum creatinine values also remained stable over three years in the 70% of patents in the high TAC peak (>20 ng/ml) subgroup (1.4±0.4 vs 1.6±1.2 mg/dL).
Patients who took TAC with food under observation on a single occasion showed an overall 30-40% reduction in peak levels and calculated AUC. In some, TAC levels were never more than 10 ng/mL during the entire dosing cycle. Even with food avoidance, predicting TAC exposure without measuring "peaks" was not possible. Between the low peak and high peak cohorts, peak levels differed by 50-100% at different time points, but trough levels remained the same at 8-10 ng/ml. By 3 years, daily TAC doses actually trended higher in the "low peak" group (5.2 ± 2.0 vs 6.6 ± 4.8 mg/day).
Conclusions: Increased TAC exposure was associated with a low rate of DSA formation, no overt nephrotoxicity, (a stable serum creatinine) and minimal viral infection. Food avoidance and measurement of TAC peak levels are necessary to predict and optimize TAC exposure. Further studies to optimize the use of this powerful immunosuppressive agent are needed.
To cite this abstract in AMA style:Hsu T, Yin J, Awdishu L, Kerr J, Steiner R. Increasing Tacrolimus Exposure to Minumize Chronic Rejection: How Can We Do It? What Are the Risks? [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/increasing-tacrolimus-exposure-to-minumize-chronic-rejection-how-can-we-do-it-what-are-the-risks/. Accessed December 1, 2023.
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