Long-term Deterioration of Kidney Allograft Function

描述(由申请人提供)：我们计划进行一项多中心研究，以准确描述晚期肾移植失败的自然历史，并剖析导致晚期功能恶化和移植物丢失的个体。以前的研究和目前的文献都将大多数慢性移植物功能障碍(CGD)归因于一种称为慢性排斥(CR)或慢性移植物肾病(CAN)的过程。大多数有这种诊断的受者在他们的临床病程后期(如果有的话)都接受了活检，当时的组织学结果是非特异性的。我们的重点是检验这一假设，即CGD通常可归因于可定义的因素，而不是一种神秘的、不可定义的力量，即CR。确定个体因素将使干预试验的未来发展成为可能。我们的假设是：1)有多个可定义的实体导致CGD(和移植物丢失)；2)这些实体可以通过临床、放射学、血清学和病理学研究加以区分。3)CGD的进展是由于可识别的、当前正在操作的损伤过程，而不是既往损伤的结果。这笔赠款的具体目的是：1)在以前的德克萨斯州横断面队列中，确定移植物最初功能障碍时的临床、实验室和病理学研究(常规组织学、免疫组织学、特殊染色)是否允许定义不同的临床病理实体(可能具有不同的临床病程)；2)在前瞻性队列中，确定初始移植物功能障碍时的临床、实验室和病理研究(常规组织学、免疫组织学、特殊染色)是否将确认不同实体的定义；3)确定纤维化活动和/或炎症的标志物、抗人白细胞抗体(HLA)抗体的存在或其他临床相关性是否可以确定与CGD进展和进展速度相关的特定病理生理特征。明确临床病理实体(以及它们各自的临床过程)将为未来CGD的研究提供一个知识基础。

DESCRIPTION (provided by applicant): We plan a multi-center study to accurately describe the natural history of late kidney transplant failure, and to dissect out individual entities leading to late deterioration of function and to graft loss. Previous studies, and the current literature, attribute most chronic graft dysfunction (CGD) to a process called chronic rejection (CR) or chronic allograft nephropathy (CAN). Most recipients with this diagnosis have undergone biopsy late in their clinical course (if ever) at which time the histologic findings are non-specific. Our focus is to test the hypothesis that CGD is usually attributable to definable factors and not to a mysterious indefinable force known, as CR. Defining individual factors will permit future development of intervention trials. Our hypotheses are: 1) there are multiple, definable entities leading to CGD (and graft loss); 2) these entities can be differentiated by clinical, radiological, serologic, and pathologic studies. 3) progression of CGD is due to an identifiable, currently operating injurious process and not the consequence of a past injury. Specific Aims of this grant are to: 1) determine, in a previously tx cross-sectional cohort, whether clinical, laboratory, and pathologic studies (conventional histology, immunohistology, special stains) at the time of initial graft dysfunction will allow definition of different clinico-pathologic entities (possibly with differing clinical courses); 2) determine, in a prospective cohort, whether clinical, laboratory, and pathologic studies (conventional histology, immunohistology, special stains) at the time of initial graft dysfunction will confirm the definition of different entities (possibly with differing clinical courses); 3) determine whether markers of fibrogenic activity and/or inflammation, the presence of anti-human leukocyte antibody (HLA) antibodies, or other clinical correlates can define specific pathophysiologic features that correlate with progression and with the rate of progression of CGD. Defining clinico-pathologic entities (and their individual clinical courses) will provide a knowledge base for future studies of CGD.