Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the response to corticosteroid therapy and renal allograft survival. We demonstrated that steroid resistance is a multifactorial condition, in which both immunological and non-immunological factors are involved. Response to steroid therapy correlates with the expression level and characteristics of allograft infiltrating T cells and macrophages, indicating that steroid resistance resides in specific cell populations and is not a feature of all lymphocytes. In addition, zinc regulation plays a role in the response to corticosteroids. Increased expression of zinc-regulating molecules may diminish the zinc-requiring anti-inflammatory effects of corticosteroids. Therefore, kidney transplant recipients may benefit from additional zinc intake to optimize steroid signaling. Furthermore, we demonstrated that a multivariate prediction model, containing biomarkers related to different aspects of corticosteroid signaling, offers the best prognostic value for assessing steroid response. Finally, we demonstrated that determination of S100A8 and S100A9 expression levels in renal allograft tissue can be used for assessing the risk of renal allograft loss over time.UBL - phd migration 201
