LONG-TERM DETERIORATION OF KIDNEY ALLOGRAFT FUNCTION (DEKAF)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当今临床肾移植（ktx）的两个主要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失败目前是美国终末期肾病（ESRD）的第三大原因，并且返回等待名单的接受者导致器官短缺。 在过去的十年里，人们希望减少急性排斥反应（AR）的发生率将减少LGL。 事实上，现代免疫抑制剂的使用已使ktx后一年的AR率在许多中心降低至<10%;这与长期功能（GFR斜率）的改善有关，也改善了，可能与新方案对排斥反应的上级控制有关。 尽管取得了这些进展，但LGL仍然是一个问题：2003年，近4 500名接受ktx治疗的患者重新接受透析治疗，其中大多数是晚期（治疗后1年以上）。 此外，移植物存活率的改善已经趋于稳定。 因此，我们提高了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。 本研究的长期目标是了解和减少长期ktx恶化。 本研究的具体目的是：1）在先前的ktx横断面队列中，确定最初移植物功能障碍时的临床、实验室或病理学研究是否定义了临床病理学实体; 2）在前瞻性队列中，确定最初移植物功能障碍时的临床、实验室和病理学研究是否定义了不同的实体;和3）确定纤维化活性和/或炎症的标记物、抗人白细胞抗原抗体的存在或其它临床相关物是否可以确定慢性移植物功能障碍的进展概率和进展速率。

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.