Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation

J Nephrol. 2016 Apr;29(2):269-276. doi: 10.1007/s40620-015-0230-0. Epub 2015 Sep 15.

Abstract

Aims: The purpose of this study is to investigate tacrolimus trough-level variability from 3 to 12 months following transplantation and its association with allograft survival in renal transplant recipients.

Materials and methods: In this observational cohort study, tacrolimus trough-level variability was used as the predictor of all-cause allograft failure (defined as return to dialysis) and patient survival (all-cause mortality).

Results: In total, 394 transplants were included in the analysis. Sixty-two transplants failed during the study. Tacrolimus trough-level variability across quartile groups were: Q1 median variability 12.5 %, range 4.76-15.71 % (n = 99), Q2 median variability 18.17 %, range 15.74-21.29 % (n = 96), Q3 median variability 24.63 % range 21.42-28.88 % (n = 100), Q4 median variability 36.91 %, range 28.91-81.9 % (n = 99). Higher tacrolimus trough-level variability was associated with inferior allograft survival in univariate models [hazard ratio per quartile increase (HR), 1.46, 95 % CI 1.16-1.83, p value = 0.001] and multivariate models (HR 1.36, 95 % CI 1.05-1.78, p value = 0.019). Higher tacrolimus trough-level variability was not associated with patient survival; univariate model (HR 1.25, 95 % CI 0.90-1.74, p value = 0.17), multivariate model (HR 1.25, 95 % CI 0.86-1.83, p value = 0.23).

Conclusions: Inferior renal allograft survival was observed in recipients with higher variability in tacrolimus trough-levels.

Keywords: Kidney; Tacrolimus; Transplantation; Variability.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Allografts
  • Chi-Square Distribution
  • Drug Monitoring
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood*
  • Kaplan-Meier Estimate
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Registries
  • Renal Dialysis
  • Risk Factors
  • Tacrolimus / administration & dosage
  • Tacrolimus / blood*
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Tacrolimus