Mechanisms and risk assessment of steroid resistance in acute kidney transplant rejection

Ever since the first successful kidney transplantation, the occurrence of acute rejection has been a dominant risk factor for adverse graft outcome, as it is associated with reduced graft survival and the development of chronic transplant dysfunction. Although the majority of acute renal allograft rejection episodes can be adequately treated with glucocorticoid therapy, 25 to 30% of the rejection episode cannot be reversed with glucocorticoids alone. At present, the diagnosis of steroid resistance primarily relies on post-transplantation follow-up of clinical parameters reflecting renal allograft function. However, it remains difficult to predict the response to the response to antirejection treatment. Prediction of steroid resistance could prevent unnecessary exposure to high-dose corticosteroid therapy and avoid the development and progression of irreversible nephron. This impact of steroid-refractory rejection on graft integrity stresses the need for tools to assess the response to AR treatment in an early stage. Here, we discuss our current understanding of resistance to anti-rejection treatment with glucocorticoids, and provide an overview of biomarkers for the detection and/or prediction of steroid resistance in kidney transplantation.