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Abstract: FR-PO790

The Number of Episodes of Subtherapeutic Tacrolimus Levels During the First Year Post Transplant Is Independently Associated With Reduced Graft Survival

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Rozen-zvi, Benaya, Rabin Medical Center, Petah Tikva, Central, Israel
  • Bielopolski, Dana, Rabin Medical Center, Petah Tikva, Central, Israel
  • Rahamimov, Ruth, Rabin Medical Center, Petah Tikva, Central, Israel
Background

Multiple studies have shown that tacrolimus (TAC) trough level variability is associated with reduced graft survival. However, specific patterns of TAC level that are associated with adverse outcome were not identified. In this study we sought to evaluate the association between the number of episodes of sub therapeutic TAC level during the first year after transplantation and graft outcome.

Methods

a single center retrospective cohort study including all kidney transplanted patients between 2001 and 2017.inclusion criteria were immunosuppression with with TAC and graft survival of more than one year. An Episode of sub therapeutic TAC level was defined as any value below 6 ng/ml during the first year, following a value above 6 ng/ml. exposure variable was the number of episodes of Tac sub therapeutic levels with cap of six (all patients with six or more episodes were categorized as having six episodes). Univariate and multivariate Cox model were used to evaluate the primary outcome of death censored graft loss. Tac level variability during the first year was included in the multivariate model.

Results

the study included 1305 patients, the mean age was 49.5±14.8 years and 884(67.7%) of them were men. The median number of sub therapeutic Tac level episodes was 1 (IQR 0-3) and 327 (25.1%) patients had no sub therapeutic Tac levels during the first year. Increased number of sub therapeutic Tac level episodes was associated with reduced graft survival (Hazard Ratio (HR), 1.41 per episode, 95% Confidence Interval (CI) 1.27-1.55 ,p<0.001). the results were not significantly changed after multivariate adjustment (HR, 1.23 per episode, 95% CI 1.09-1.37, p=0.001). when the composite outcome of graft loss and mortality was evaluated the results were comparable (HR, 1.23 per episode, 95% CI 1.15-1.32, p<0.001) and (HR, 1.16 per episode, 95% CI 1.07-1.26, p<0.001) for univariate and multivariate analysis respectively.

Conclusion

Episodes of sub therapeutic Tac level are associated with reduced graft survival independent of Tac level variability. Studies evaluating the effect of strategies to reduce the number of sub therapeutic Tac levels on graft outcomes might be helpful.