title: Identifying endpoints to predict the influence of immunosuppression on long-term kidney graft survival.
abstract: Identifying a short-term endpoint for use in clinical trials that accurately reflects the influence of specific immunosuppressive regimens on long-term kidney graft survival is challenging. The number, timing, type (T-cell-mediated or antibody mediated), and severity of biopsy-proven acute rejection (BPAR) episodes in terms of histological changes and functional impact are highly influential for graft prognosis, and a crude measure of overall acute rejection incidence alone is unlikely to be a robust predictor of graft outcome. A series of studies has shown remarkably consistent results in terms of the cutoff point for one-yr renal function which predicts poor long-term graft survival, indicating that a threshold of 50 mL/min/1.73 m(2) is likely to be appropriate. Estimated glomerular filtration rate at one yr post-transplant discriminates effectively among immunosuppressive regimens with regard to graft survival, primarily calcineurin inhibitor reduction strategies. Several other factors that can affect graft survival, such as pathological changes in the graft, may be partly influenced by the immunosuppressive regimen, but the contribution of drug therapy is difficult to define. A combined approach in which both treated BPAR and renal function at one yr are used to assess novel immunosuppressive regimens appears to be promising as the emphasis shifts toward sustaining kidney allograft survival over the long term.
authors.affiliation: Kidney and Pancreas Transplant Programs, Division of Nephrology, Medical University of South Carolina, Mount Pleasant, SC, USA.
authors.forename: Titte R
authors.initials: TR
authors.lastname: Srinivas
authors.affiliation: Renal Transplant Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Oppenheimer
mesh_terms: D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D011379:Prognosis
chemical_list: D007166:Immunosuppressive Agents
keywords: acute rejection; biopsy-proven acute rejection; clinical trial; endpoint; glomerular filtration rate; kidney transplantation; long term; renal function