PATHOPHYSIOLOGY OF CHRONIC ALLOGRAFT NEPHROPATHY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（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。所列机构为中心，不一定是研究者所在机构。> 60岁的老年尸体供体不愿意用于肾移植（Tx），因为已显示老年肾同种异体移植物与短半衰期相关。我们现拟阐明老年尸体移植受者肾脏衰老与慢性移植物肾病（CAN）加速之间的关系。我们将使用生理学和形态学技术来阐明参加我们移植后诊所的移植受者的肾小球功能和结构。我们希望确定年轻（<40岁）和老年（55岁）肾供体的受体之间是否存在定性或定量差异。这是对我们的纵向（系列）研究"肾衰老和移植"的横断面补充，该研究已获得GCRC批准（NIH资助DK064697）。 我们的目的是检验以下四个假设：（1）肾小球绝对数量的减少减少了滤过表面积（S）的可用性。(2)这（S）被肾小球进一步损害，所述肾小球由于整体肾小球硬化或与近端小管分离而不再能够形成肾小球滤液（所谓的"无小管肾小球"）。(3)由于肾小球毛细血管壁（k）的水力渗透性受损和/或滤过表面积减少，其余未闭和滤过肾小球的超滤系数（Kf）降低。(4)肾脏衰老和CAN的结合导致老年供体同种异体移植物中肾小球肾炎的进行性和增加性。我们将使用生理学和形态学技术，沿着数学建模和MRA来确定滤过能力和肾小球数量。 将要求接受单个年轻肾脏、单个老化肾脏或两个老化肾脏移植且Tx肾脏仍有功能的CAN受试者参加本研究。

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. Elderly cadaveric donors >60 yrs-old are reluctantly used for kidney transplantation (Tx), because an aged renal allograft has been shown to be associated with a short half-life. We now propose to elucidate the relationship between renal senescence and acceleration of chronic allograft nephropathy (CAN) in recipients of aged cadaver transplants. We will use physiological and morphometric techniques to elucidate glomerular function and structure in transplant recipients attending our post-transplant clinic. We wish to determine whether there are qualitative or quantitative differences between recipients of youthful (<40 yr) and aged (55 yr) kidney donors. This is a cross-sectional addition to our longitudinal (serial) study entitled "Renal Senescence and Transplantation," already approved by the GCRC (NIH grant DK064697). Our aim is to test the following four hypotheses: (1) That a reduction in the absolute glomerular number curtails the availability of surface area for filtration (S). (2) That (S) is further compromised by glomeruli that are no longer able to form glomerular filtrate by virtue of either global glomerulosclerosis or separation from the proximal tubule (so called "atubular glomeruli"). (3) That the ultrafiltration coefficient (Kf) of the remaining patent and filtering glomeruli is depressed because of impaired hydraulic permeability of glomerular capillary walls (k) and/or reduction in filtration surface area. (4) A combination of renal senescence and CAN leads to progressive and incremental glomerulopenia in allografts from aged donors. We will use physiologic and morphometric techniques, along with mathematical modeling and MRA to determine filtration capacity and glomerular number. Subjects with CAN, who underwent transplantation with a single youthful kidney, a single aged kidney, or two aged kidneys, and whose Tx kidneys are still functioning will be asked to participate in this study.