Withdrawal of CsA from SRL maintenance therapy has

also been shown to be a safe and LEE011 research buy effective alternative to continuous therapy with CsA and SRL [3] and [11]. EVR combined with reduced-dose CsA has been shown to be well tolerated, with low efficacy failure and better renal function, compared with EVR combined with full-dose CsA [10]. Further, EVR with progressive reduction in CsA dose of up to 60% at 1 year resulted in similar efficacy and a trend towards improved renal function, compared with standard-exposure CsA in combination with mycophenolic acid (MPA) [12]. TAC-based regimens, however, are the most frequently used regimens in clinical practice for both initial and maintenance immunosuppression (> 80% and > 70%, respectively, of renal transplant recipients). Between 1998 and 2009, the use of TAC increased from around 26% to 88% [13]. As a result, TAC has largely supplanted CsA over the past 10 years. Indeed, the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines for the care of kidney transplant recipients recommend the use of CH5424802 in vitro TAC as the first-line CNI for initial maintenance therapy in combination with an antiproliferative agent, with or without corticosteroids [14]. The need to develop regimens that allow TAC minimization is, therefore, an area of clinical importance. Another important consideration is that CNIs have a narrow

therapeutic window (exposure for efficacy is close to that causing toxicity), with drug over- and under-exposure leading to potentially serious consequences. Achieving the optimal dose in clinical practice is often challenging because of inter- and intra-individual CNI pharmacokinetic variations [2]. In particular, after a CNI dose there is considerable variability in blood–drug concentrations between individuals [15]. Therefore, to optimize treatment outcomes careful therapeutic drug monitoring (TDM) is required [2]. Most clinicians prescribing

CNIs use blood concentration measurements to guide dosing. When administering TAC, trough concentration (C0) monitoring is commonly used as a basis for individualizing treatment [15] and [16] because, unlike CsA, there is a relatively good correlation between TAC exposure and C0. TDM has been recommended Enzalutamide solubility dmso for many other immunosuppressive drugs. A consensus group concluded that although routine TDM of MPA is not recommended, specific patient groups such as those at heightened immunologic risk, undergoing minimization or withdrawal of immunosuppressive therapy, or experiencing altered hepatic, renal, or bowel function could benefit from TDM [17]. There is, however, currently no evidence that MPA TDM has an impact on graft outcomes or patient survival. As mTOR inhibitors have a narrow therapeutic window and variable oral bioavailability, TDM is also advocated for these drugs [18].