Abstract
Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.
Highlights
Immunosuppressive drugs and the therapies based on these drugs have markedly improved the graft survival and function, which has enabled successful renal transplantation
Calcineurin inhibitors (CNIs), steroids, mycophenolate mofetil (MMF), basiliximab (Bx), and everolimus (EVL) are used in combination at renal transplant centers to reduce the dose of each drug and side effects while maintaining immunosuppressive effects
We focused on individual lymphocyte sensitivity to GCs as an index to predict the pharmacodynamic efficacy of GCs in renal transplantation [11]
Summary
Immunosuppressive drugs and the therapies based on these drugs have markedly improved the graft survival and function, which has enabled successful renal transplantation. Calcineurin inhibitors (CNIs), steroids (glucocorticoids: GCs), mycophenolate mofetil (MMF), basiliximab (Bx), and everolimus (EVL) are used in combination at renal transplant centers to reduce the dose of each drug and side effects while maintaining immunosuppressive effects. Several studies have shown that GC reduction/withdrawal could be a safe standard for immunosuppressive therapy in low immunological risk recipients [2,3,4,5,6,7]. Some studies have shown that GC reduction/withdrawal was associated with an increase in the incidence of acute graft rejection (AR) and a more rapid deterioration of graft function [8,9,10]. The problem is that there is no clear index to predict patients who can have their dose of GCs safely reduced and/or withdrawn at present
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