Tacrolimus Concentration-to-Dose Ratios in Kidney Transplant Recipients and Relationship to Clinical Outcomes.

INTRODUCTION: One factor impacting tacrolimus interpatient variability is the presence of CYP3A5 polymorphisms. Low tacrolimus concentration-to-dose ratios (CDRs), or rapid metabolizers (RMs), have been associated with poor graft function outcomes and higher biopsy-proven acute rejection (BPAR) rates in a predominantly white population. Pretransplant CYP genotyping is not routinely conducted, and therefore only a small number of studies have assessed the use of tacrolimus CDRs as a surrogate for metabolism. We explored differences in outcomes between patients with low tacrolimus CDRs and high tacrolimus CDRs (i.e., nonrapid metabolizers [NRMs]) in a diverse patient population. OBJECTIVE: To determine the relationship between tacrolimus CDRs and graft and patient outcomes in kidney transplant recipients at a large transplant center between 2006 and 2016. METHODS: Inclusion criteria consisted of adult kidney transplant recipients who received rabbit antithymocyte globulin induction followed by a maintenance regimen of tacrolimus, mycophenolate, and prednisone. The primary end point was BPAR at 1 year. Secondary end points included graft survival, patient survival, and toxicities. Determination of clusters was conducted using the two-step cluster analysis with a defined two-cluster distribution. Kaplan-Meier survival curves were created using the log-rank test. RESULTS: The NRM cluster consisted of 322 patients with a mean CDR of 2.91 ng/ml/mg. The RM cluster consisted of 932 patients with a mean CDR of 1.14 ng/ml/mg. The BPAR at 1 year posttransplant was 3.7% in the NRM cluster and 3.6% in the RM cluster (p=0.95). Death at 5 years was higher in the NRM group compared with the RM group for unknown reasons (p=0.03). Differences in the incidence of posttransplant toxicities were not statistically significant at any time point, except for increased rates of cutaneous cancer at 5 years and cardiovascular disease overall in the NRM group. CONCLUSION: Tailoring tacrolimus therapy early posttransplant based on CDR is not supported by the findings in this study.

Impact of a pharmacist-led vaccine recommendation program for pediatric kidney transplant candidates.

Pediatric transplant recipients commonly have deficient vaccination status at the time of transplantation. Utilizing transplant pharmacists to improve vaccination rates has not previously been described. This single-center, retrospective study evaluated the impact of transplant pharmacist interventions on the completion rate of vaccination schedules at time of kidney transplant. Patients who received pharmacist-led vaccination recommendations prior to transplant were compared to patients without pharmacist recommendations. Forty-seven pediatric patients were included: 24 intervention patients and 23 control patients. The median percentage of up-to-date vaccinations at time of transplant was significantly higher in intervention group (91%; IQR 86%-100%) vs. control group (80%; IQR 71%-80%) (P<.0001). The median change in up-to-date vaccinations from time of evaluation to time of transplant was also significantly higher in the intervention group (7.5%) compared to the control group (0%) (P<.0001). There was no difference in live vaccination rates. No patients in either group were readmitted for a vaccine-preventable disease within 6 months post-transplant. With pharmacist intervention, significantly more patients were up to date with vaccination schedules at the time of transplant. These results suggest that a transplant pharmacist may serve as a valuable resource to increase vaccination schedule compliance between time of evaluation and transplantation.