Immune Minimization Strategies in Renal Transplantation

Abstract

Very low early rejection rates and excellent short-term kidney allograft outcomes have been the mainstay of forwarding the field of Kidney Transplantation in the last few decades. This progress is mainly achieved by using the current armamentarium of maintenance immunosuppression in different combinations and dosages of calcineurin inhibitors (CNI), corticosteroids and antiproliferative drugs. Metabolic risks and nephrotoxicity of CNIs has led to a search for strategies to minimize their use. Similarly, metabolic risks, mood abnormalities and Cushing-like side effects of steroids have forced physicians and patients alike to try to minimize their use in transplantation. Here, we review the most recent randomized controlled trials of minimization of CNI/steroids in a manner (with incident immunologic risks, state of net immunosuppression and side- effects) that may be helpful to choose the best strategy for the individual patient. New trials testing minimization strategies should include in their design, an assessment of the impact of minimization on development of donor specific antibodies and antibody-mediated rejection as well as long-term outcomes.

TCL1A, B Cell Regulation and Tolerance in Renal Transplantation

“…Continuous improvement in transplantation outcomes is due in part to better clinical management in the instauration of life-long immunosuppressive (IS) therapy, which is required to control recipients' alloimmune response and prevent graft rejection [1]. In addition, many attempts have been made to minimize IS treatments [2], which are still sources of important side effects, including infection, cancer, nephrotoxicity and metabolic complications [3][4][5][6] with insufficient benefits for long-term graft survival [7]. In this context, tolerance defined as allograft acceptance in the absence of immunosuppression represents the ultimate goal in solid organ transplantation, as it avoids IS treatment side effects and thereby improves the recipient's quality of life.…”

Cell therapy in muscular dystrophies: many promises in mice and dogs, few facts in patients

“…control or avoid acute rejection by methods with less secondary effects, in the case of the allotransplantation of cells from a normal donor to a MD patient. The closest strategy to the current clinical reality is the refinement of the immunosuppression protocols, ideally by the development of immunosuppression minimization [121]. The other possibility, in which up to now they have been little clinical success, is through efficient strategies of immune tolerance, a major goal in the global field of transplantation [122].…”

The use of novel diagnostics to individualize immunosuppression following transplantation

“…Indeed, these side effects contribute to the so far unsatisfactory long‐term graft and patient survival . Although scientists and also industry continuously search for novel immunomodulatory therapies with similar effectiveness but decreased toxicity, it is generally accepted that IS minimization or even complete withdrawal might help to improve long‐term outcomes in a significant proportion of patients . Thus, over the last 10–15 years, many researchers worldwide have tried to identify biomarkers or functional assays suitable for an identification of patients eligible for IS minimization or weaning .…”