CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

J. Hougardy, M. Kianda, A. Massart, A.D. Hoang, D. Mikhalski, M. Wissing, N. Broeders, D. Abramowicz
Nephrology, Hopital Erasme, Brussels/BELGIUM

Body: Introduction: Advagraf® is a slow release form of tacrolimus with oncedaily formulation. Potential advantages of Advagraf® are better adherence, lower intersubject tacrolimus exposure variability and a safer profile by avoiding toxic peak concentrations. In thepresent study, we evaluated the required daily doses of tacrolimus and subsequent blood levels upon conversion from Prograft® to Advagraf® among kidney transplant recipients. Material andmethods: We retrospectively reviewed data from 59 patients for whom a switch from Prograft® to Advagraf® was made between september 2008 and november 2009. Mean age of patients was 49.8years (min-max: 19.4-77.8). 59 % of patients were male. Mean duration since transplantation was 4.02 years (0.07-18.04). Tacrolimus daily doses (per kg of body weight) and concomittant blood levelswere analysed at several time points comprised between 3 months before and 6 months after conversion. Results: Switching from Prograft® to Advagraf® resulted in significant decrease intacrolimus blood levels (from 8.07 +/- 1.78 ng/ml to 6.62 +/- 1.76 ng/ml 6 months after conversion, P <0.0001). 29 % of the patients showed a decrease of 20% or more in their tacrolimus bloodlevels at 6 months. This is in sharp contrast with a significant increase in concomitant tacrolimus daily doses (from 0.077 +/- 0.044 mg/kg to 0.090 +/- 0.045 mg/kg 6 months after conversion,P<0.0001). Nearly 30 % of patients had an increase of tacrolimus daily dose of more than 20% at 6 months. These variations in both blood levels and daily doses of tacrolimus were not observed in acontrol group treated with Prograft® during the same period. Subgroup analyses showed that diabetes, treatment with protons-pump-inhibitors and obesity were associated with a more profoundreduction in tacrolimus blood levels despite adjustement of Advagraf® daily doses. Concomittant treatment with MMF did not modify the decrease in tacrolimus blood levels. While overall creatininevalues remained stable over time, one patient developed acute rejection in association with low Advagraf® levels. Conclusions: Contrary to the manufacturer instructions, we found asignificant decrease in tacrolimus exposure after switching to Advagraf®. We suggest that the switch from Prograft® to Advagraf® should be performed under close medicalsupervision.

Disclosure: All authors have declared no conflicts of interest.