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

• Published in: Journal of nephrology 2016-04, Vol.29 (2), p.269-276
• Main Authors: O’Regan, John A., Canney, Mark, Connaughton, Dervla M., O’Kelly, Patrick, Williams, Yvonne, Collier, Geraldine, deFreitas, Declan G., O’Seaghdha, Conall M., Conlon, Peter J.
• Format: Article
• Language: English
• Subjects: 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; Medicine; Medicine & Public Health; Middle Aged; Multivariate Analysis; Nephrology; Original Article; Predictive Value of Tests; Proportional Hazards Models; Registries; Renal Dialysis; Risk Factors; Tacrolimus - administration & dosage; Tacrolimus - blood; Time Factors; Treatment Outcome; Urology
• ISSN: 1121-8428; 1724-6059
• DOI: 10.1007/s40620-015-0230-0

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.