Background: Intrapatient trough levels variability of immunosuppressive drugs must be considered as a prognostic factor. Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitors (CNI) levels and poor long-term renal graft outcome. Recent studies suggest a lower variability when using once-daily tacrolimus compared to the classical twice-daily formulation. Our objective is to analyze the intrapatient variability observed in the blood levels of mTOR-inhibitors (mTORi) and to compared the variability of sirolimus (SRL) with that of everolimus (EVL) in transplant patients converted to an iMTORi.
Methods: We analyzed 256 adult renal transplant patients converted to an mTORi between Jan-2009 and Dec-2015 in two Spanish transplant centers. The mean post-transplant conversion time was 51,6 months. One hundred and seventeen werw converted to SRL and 139 to EVL. Coefficient of variation (CV) was calculated using at least 3 blood trough levels between 3 and 18 months postconversion. Conversions in the first postransplant year (121) and later (135) were analized separatedly. CV was correlated with graft evolution (graft survival and/or renal function).
Results: The mean and median CV of the entire group was 25,6∓13,0% and 23,7∓12,1%. SRL and EVL mean CV was 23,8% and 27,1% (p=0,04). Inthe subgroup of late conversions (>1 y) SRL and EVL-CV was 23,0% and 29,0% (p=0,008). 59,8% vs 41,7% of patients converted to SRL and EVL respectively had a CV below the median (p=0,004). No differences in graft evolution could be demonstrated between patients with high and low CV at a mean follow-up of 58,5∓21,4 months.
Conclusions: We suggest that SRL has a lower CV than EVL. This difference should probably have a prognostic significance but we have not found differences in the long-term follow-up. This might probably be a consequence of that most patients were converted in the stable postransplant phase.