Srinivas Titte R, Oppenheimer Federico
Kidney and Pancreas Transplant Programs, Division of Nephrology, Medical University of South Carolina, Mount Pleasant, SC, USA.
Renal Transplant Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
Clin Transplant. 2015 Jul;29(7):644-53. doi: 10.1111/ctr.12554.
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.
确定一个可用于临床试验的短期终点，以准确反映特定免疫抑制方案对肾移植长期存活的影响，是一项具有挑战性的任务。活检证实的急性排斥反应（BPAR）发作的数量、时间、类型（T细胞介导或抗体介导）以及根据组织学变化和功能影响所确定的严重程度，对移植肾预后有很大影响，仅用总体急性排斥反应发生率的粗略衡量指标不太可能成为移植肾结局的可靠预测指标。一系列研究在预测长期移植肾存活不佳的一年肾功能临界值方面显示出非常一致的结果，表明50 mL/min/1.73 m²的阈值可能是合适的。移植后一年的估计肾小球滤过率在不同免疫抑制方案对移植肾存活方面，主要是在钙调神经磷酸酶抑制剂减量策略方面能有效区分。其他一些可能影响移植肾存活的因素，如移植肾的病理变化，可能部分受免疫抑制方案影响，但药物治疗的作用难以界定。随着重点转向长期维持同种异体肾移植存活，采用一种将治疗后的BPAR和一年时的肾功能结合起来评估新型免疫抑制方案的综合方法似乎很有前景。
