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Abstract: FR-PO782

Interactive Impact of Tacrolimus Inter-Patient Variability and Intra-Patient Variability in Allograft Outcomes in Kidney Transplantation

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Park, Yohan, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Lee, Hanbi, Seoul Saint Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)
  • Eum, Sang Hun, Seoul Saint Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)
  • Yoon, Se-Hee, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Hwang, Won Min, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Yun, Sung-Ro, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Yang, Chul Woo, Seoul Saint Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)
  • Chung, Byung ha, Seoul Saint Mary's Hospital, Seocho-gu, Seoul, Korea (the Republic of)
Background

Concentration to dose ratio (CDR) of tacrolimus (TAC) is an index of inter-patient variability that reflects tacrolimus metabolism, and whether it influences allograft outcomes is controversial in kidney transplantation (KT). This study analyzed the effect of TAC inter-patient variability combined with TAC intra-patient variability (IPV) on allograft outcomes.

Methods

In total, 1,080 patients with immunologic low risk were enrolled. Inter-patient variability was calculated as the mean value of CDRs up to 3 months after KT, and was defined as rapid metabolizer (RM) if it was lower than 1.05. IPV was calculated as the time-weighted coefficient variability (TWCV) of the TAC-trough level (C0) up to 1 year after KT, and was defined as high IPV group if it was higher than 30%. According to CDR and TWCV, patients were divided into 4 groups: Low IPV/Non-rapid metabolizer (NRM), High IPV/NRM, Low IPV/RM, and High IPV/RM.

Results

Death-censored graft loss (DCGL) rates were 5.5% (25/452) in the Low IPV/NRM group, 10.5% (38/375) in the High IPV/NRM group, 5.7% (6/106) in the Low IPV/RM group, and 19.1% (28/147) in the High IPV/RM group, which was the significantly highest in the High IPV/RM group (P < 0.001). In Cox regression analysis, the odds ratio (OR) of High IPV/RM was 3.06 (1.78-5.25), which was observed as a significant risk factor. In the analysis in which the TAC time weighted average value was adjusted, High IPV/RM was remained as a significant risk factor with OR 2.60 (1.41-4.79).

Conclusion

High TAC-IPV in patients with low CDRs in the early post-transplantation period is thought to have a significant adverse effect on the allograft outcomes. Stratification is required for patients with RM characteristics (low CDRs) in the clinical field, and more careful tacrolimus dose adjustment efforts are needed in these patients.