Thursday 14 march 2019
12:45 - 12:48h
Categories: Klinisch, Postersessie
Parallel session: Postersessies 2 - Clinical
M.A.A. van der Veer1, N. Nangrahary2, D.A. Hesselink3, N.S. Erler4, H.J. Metselaar1, T. van Gelder3, S. Darwish Murad1.
1Dept. of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam. 2Dept. of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam. 3Dept. of Internal Medicine, Erasmus University Medical Center, Rotterdam. 4Dept. of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Background: A high intrapatient variability in tacrolimus exposure is associated with impaired long-term clinical outcome after kidney transplantation. It remains to be determined if a high tacrolimus intrapatient variability is equally detrimental for liver transplant recipients. The objective of this study was to investigate the association between intrapatient variability in tacrolimus exposure and immune-mediated graft injury after liver transplantation.
Methods: For 326 liver transplant recipients, transplanted between 2000 and 2015, tacrolimus intrapatient variability was calculated from at least 5 tacrolimus trough samples obtained between month 6 and 18 after liver transplantation and was expressed as the coefficient of variation. The primary composite endpoint consisted of immune-mediated graft injury (chronic rejection, biopsy proven late-acute rejection and suspected late-acute rejection) after month 6 post-liver transplantation. Secondary outcomes were the association between tacrolimus intrapatient variability on (1) loss of renal function per year of follow-up and (2) cytomegalovirus viremia after month 6 post-liver transplantation.
Results: Of the 326 included liver transplant recipients, 70 patients (21.5%) reached the primary endpoint. Median tacrolimus coefficient of variation was 28%. There was no significant difference in reaching the primary composite endpoint between the low and high tacrolimus variability group (p=0.068). Tacrolimus intrapatient variability modeled as a continuous variable remained non-significantly associated with the risk of reaching the primary endpoint in a multivariable analysis. MELD-score pre-transplantation and the number of acute rejections were identified as independent predictors for immune-mediated graft injury (p=0.049, p=0.016). For the secondary endpoints, a higher tacrolimus variability in combination with a low kidney function at baseline (eGFR < 40 ml/min) was associated with greater loss of renal function per year of follow-up (p=0.007). Tacrolimus variability was not associated with late cytomegalovirus viremia.
Conclusions: High intrapatient variability in tacrolimus exposure beyond month 6 post-liver transplantation was not found to be associated with immune-mediated graft injury.