LONG-TERM DETERIORATION OF KIDNEY ALLOGRAFT FUNCTION (DEKAF)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前临床肾移植面临的两大问题是移植物晚期丢失(LGL)和器官短缺。事实上，这些问题是相互关联的-KTX衰竭目前是美国终末期肾病(ESRD)的第三大原因，而重新进入等待名单的接受者导致了器官短缺。在过去的十年里，人们希望通过减少急性排斥反应(AR)的发生率来减少LGL。事实上，在KTX后的最后一年里，许多中心使用现代免疫抑制药物使AR率下降到10%；这与长期功能的改善(GFR的斜率)也有所改善，可能与使用新的方案更好地控制排斥反应有关。尽管取得了这些进展，LGL仍然是一个问题：2003年，近4500名KTX接受者重返透析，其中大多数人晚了(&gt；TX后一年)。此外，移植物存活率的改善已经停滞不前。因此，我们改善了AR率和早期结果，但LGL仍然是一个问题；我们以前的概念化为有效干预提供了不充分的基础。 这项研究的长期目标是了解和减少KTX的长期恶化。这项研究的具体目的是：1)在以前的KTX横断面队列中，确定最初移植肾功能障碍时的临床、实验室或病理研究是否确定临床病理实体；2)在前瞻性队列中，确定最初移植肾功能障碍时的临床、实验室和病理研究是否定义不同的实体；以及3)确定纤维化活动和/或炎症的标志物、抗人类白细胞抗原抗体的存在或其他临床相关因素是否可以确定慢性移植肾功能障碍的进展概率和进展率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The two major problems in clinical kidney transplantation (ktx) today are late graft loss (LGL) and the shortage of organs. In fact, these problems are interrelated - ktx failure is currently the 3rd leading cause of end stage renal disease (ESRD) in the U.S. and recipients returning to the waiting list contribute to the organ shortage. For the past decade it was hoped that decreasing the incidence of acute rejection (AR) would reduce LGL. In fact, the use of modern immunosuppression has decreased AR rates during the last year post-ktx to <10% at many centers; this has been associated with improvement in long-term function (the slope of the GFR) has also improved, perhaps related to superior control of rejection with newer protocols. Despite these advances, LGL continues to be a problem: almost 4,500 ktx recipients returned to dialysis in 2003, most of them late (>1 year post-tx). Furthermore, improvements in graft survival have plateaued. Thus, we have improved AR rates and early outcomes but LGL remains a problem; our previous conceptualization provides an inadequate basis for effective intervention. The long-term goal of this study is to understand and reduce long-term ktx deterioration. The specific aims of the study are to 1) determine, in a previously ktx cross-sectional cohort, whether clinical, laboratory, or pathologic studies at the time of initial graft dysfunction define clinico-pathologic entitites; 2) determine, in a prospective cohort, whether clinical, laboratory, and pathologic studies at the time of initial graft dysfunction define different entitites; and 3) determine whether markers of fibrogenic activity and/or inflammation, the presence of anti-human leukocyte antigen antibodies, or other clinical correlates can define the probability of progression and the rate of progression of chronic graft dysfunction.