Challenges in the use of glucocorticoids in transplantology

Abstract

Introduction. Glucocorticoids (GCs) have long time played a key role in solid organ transplantation (SOT), thanks to their strong anti-inflammatory and immunosuppressive effects. However, their use presents a significant drawback: while they help prevent rejection, they also bring a wide range of side effects that can impact long-term patient health. This study explores the challenges of using GCs in transplantation, focusing on their effects on graft survival, the risks associated with their prolonged use, and potential strategies to minimize their downsides. Materials and Methods. A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar databases. Studies published between 2011 and 2025 were analyzed using keywords such as "glucocorticoids," "solid organ transplantation," "immunosuppression," and "side effects." We extracted relevant data on GC mechanisms, benefits, drawbacks, and emerging alternatives to improve transplant outcomes. Results. Glucocorticoids remain a staple in SOT, used for induction and maintenance therapy as well as for treating acute rejection episodes. However, their widespread use is not without consequences. Patients on long-term GC therapy face an increased risk of infections, including bacterial, fungal, and viral complications. Metabolic and endocrine issues such as diabetes, osteoporosis, and adrenal insufficiency are common, while cardiovascular effects like hypertension and endothelial dysfunction add to the risks. Neurological side effects, including mood disturbances and steroid-induced psychosis, further complicate long-term management. Additionally, prolonged GC exposure may contribute to chronic allograft dysfunction, potentially jeopardizing transplant success. Given these challenges, researchers are exploring alternative approaches such as steroid-sparing regimens, targeted GC delivery via nanoparticles, and selective immunomodulators like mTOR inhibitors and IL-6 blockers to reduce toxicity while maintaining immunosuppressive efficacy. Conclusions. While GCs remain integral to SOT, their long-term use presents significant challenges. Optimizing immunosuppressive regimens through targeted therapies and personalized approaches could improve outcomes and reduce complications. Steroid-sparing strategies include rapid tapering protocols, complete steroid avoidance in low-risk patients, and combination therapies using calcineurin inhibitors, mTOR inhibitors, and monoclonal antibodies. Further research is needed to refine these approaches and enhance graft survival.