Immunosuppressive Drugs Used in Kidney Transplantation
Özet
Kidney transplantation is the most effective treatment for end-stage kidney disease (ESKD). However, the success of the transplant depends on the prevention of both early and late-stage rejection. Therefore, immunosuppressive therapy used to prevent rejection is critical for transplant outcomes. The primary goal of immunosuppression is to maximize the preservation of graft function while minimizing the risk of serious side effects, such as infection and druginduced toxicity. Immunosuppressive therapy consists of two stages: intensive "induction" therapy administered at the time of transplant, followed by lifelong "maintenance" therapy. The goal of induction therapy is to prevent the risk of acute rejection, which is highest during the early postoperative period. Agents used for induction include lymphocyte-depleting agents (e.g., anti-thymocyte globulin (ATG), alemtuzumab) and non-depleting agents (e.g., basiliximab). The patient’s immunological risk profile is essential in selecting the induction agent. For high-risk patients, more potent agents are preferred, whereas for low-risk patients, agents with a lower potential for side effects are chosen. Following induction therapy, maintenance therapy is initiated to ensure long-term graft survival. During this period, a combination therapy consisting of calcineurin inhibitors (CNIs) (tacrolimus and cyclosporine), which inhibit critical pathways in T-cell activation; antiproliferative agents (mycophenolate mofetil (MMF) and Azathioprine (AZA)); and steroids are used.Both induction and maintenance immunosuppressive regimens are personalized by considering individual factors such as the patient’s immunological risk profile, Human Leukocyte Antigen (HLA) matching, panel reactive antibody (PRA) levels, the presence of donor-specific antibodies (DSA), and infection history. Effective and safe immunosuppressive management is achieved through "Therapeutic Drug Monitoring" (TDM). Regular monitoring of blood levels, especially for drugs with a narrow therapeutic index like CNIs, prevents both drug toxicity and the development of rejection due to subtherapeutic levels.
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