The Coefficient of Variability is the Same in the mTOR-inhibitors?

Abstract

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.