Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation.

BACKGROUND: Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation. METHODS: We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included. RESULTS: The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated. CONCLUSIONS: High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.

Lung Transplantation and the Era of the Sensitized Patient.

Long term outcomes in lung transplant are limited by the development of chronic lung allograft dysfunction (CLAD). Within the past several decades, antibody-mediated rejection (AMR) has been recognized as a risk factor for CLAD. The presence of HLA antibodies in lung transplant candidates, "sensitized patients" may predispose patients to AMR, CLAD, and higher mortality after transplant. This review will discuss issues surrounding the sensitized patient, including mechanisms of sensitization, implications within lung transplant, and management strategies.

Tacrolimus dose requirements in African-American and Caucasian kidney transplant recipients on mycophenolate and prednisone.

Racial differences among kidney transplant recipients may impact the total daily tacrolimus dose required to achieve therapeutic tacrolimus concentrations. Previous studies suggest that African Americans require higher doses to achieve similar therapeutic drug concentrations compared with Caucasians. Data were collected on a total of 147 de novo kidney transplant recipients. Tacrolimus total daily dose (TDD) requirements (mg/kg/d) and tacrolimus concentrations were retrospectively reviewed at discharge and at days 30, 60, and 90 after transplant. TDD requirements in African-American and Caucasian patients were 0.14 mg/kg/d and 0.11 mg/kg/d, respectively (p = 0.005), at day 30. TDD requirements at day of hospital discharge and days 60 and 90 following transplant were significantly higher in African-American patients vs. Caucasian patients, with similar tacrolimus concentrations at all time points. This study suggests that when compared to Caucasians, African Americans require significantly higher TDD of tacrolimus to achieve similar tacrolimus concentrations. These findings provide transplant clinicians with a sense of certainty to more rapidly titrate daily tacrolimus doses in African-American patients to achieve therapeutic concentrations.