Although the scarcity of clinical trials with de-novo immunosuppression has been typical over the last 2 years, several attempts have been made in drug conversion, dosing optimization, and bioequivalence. On the basis of recent clinical and animal studies, future directions of management and treatment are outlined.
Studies with new tacrolimus formulations showed better bioavailability and lower doses, which might translate into less toxicity. The long-term results of studies with costimulation blockade confirmed their safety and efficacy. Calcineurin inhibitor (CNI)-free regimens based on mTOR inhibitors were shown to be associated with increased risk of the humoral response. Therefore, ongoing trials are predominantly designed to minimize calcineurin inhibitor dose only. Biologics, such as B-cell-specific agents (bortezomib and rituximab) and complement inhibitors (eculizumab) used to treat antibody-mediated rejection, recurrence of glomerulonephritis, are shifted to more preventive applications. The pretransplant quantification of alloreactive memory/effector T cell response may help to better stratify a patient's immunologic risk and allow for drug minimization.
Despite clinical trials with innovative protocols with already established agents, tacrolimus-based and induction-based protocols have been shown to be the mainstay of immunosuppressive regimens. In the future, research aims to focus on biomarker-driven immunosuppression and cell therapy approaches.
aDepartment of Nephrology, Transplant Centre
bTransplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Correspondence to Ondrej Viklicky, MD, PhD, Department of Nephrology, Transplant Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech Republic. Tel: +420 23605 4110; fax: +420 23605 3168; e-mail: firstname.lastname@example.org