The macro- and micro- anatomy and pathology of the aging kidney

衰老肾脏的宏观和微观解剖学及病理学

基本信息

批准号：
8425058
负责人：
ANDREW David RULE
金额：
$ 63.08万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-10 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8425058
关键词：
20 year old Adult Age Aging Albumins Albuminuria Anatomy Angiography Area Arteriosclerosis Atrophic Biological Markers Biopsy Birth Blood Pressure Characteristics Chronic Kidney Failure Cicatrix Clinic Clinical Development Diagnosis Disease Elderly Endowment Evaluation Family history of Fibrosis Functional disorder Future General Population Glomerular Filtration Rate Goals Health Histologic Hypertrophy Hyperuricemia Image Injury Kidney Kidney Failure Lead Life Liver Measures Nephrons Nephrosclerosis Obesity Outcome Pathology Persons Population Study Proteins Renal function Risk Factors Sampling Scanning Serum Site Testing Tissues Tubular formation Urine X-Ray Computed Tomography age difference age related bikunin disorder risk fatty acid-binding proteins functional loss glomerulosclerosis implantation improved insight interstitial kidney cortex novel prevent public health relevance rat KIM-1 protein renal artery renal scarring response

项目摘要

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) has both a clinical description (reduced kidney function and protein in the urine) and a pathological description (nephrosclerosis as characterized by glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis). Both occur with age, but little is known about their relationship to each other. The goal of this study is to characterize age-related changes in the kidney in a large sample of living kidney donors at two sites (Mayo Clinic and Cleveland Clinic), to identify biomarkers that predict these changes, and to eventually relate renal pathology and biomarkers that detect renal pathology to clinical outcomes in future studies. Combining computed tomography (CT) scan findings (total renal cortex volume) and renal biopsy findings (glomeruli per renal cortex unit volume) allows estimation of nephron endowment (total number of nephrons a person is born with). Our central hypothesis is that with aging, progressive nephrosclerosis leads to atrophy of nephrons with cortical volume loss and scarring. This volume loss is initially compensated by hypertrophy of viable nephrons, which leads to further nephrosclerosis. Eventually, however, volume loss from nephrosclerosis overwhelms the compensatory hypertrophy of remaining nephrons and the kidneys decrease in size. Aim 1. To test the hypothesis that age, GFR, urine albumin, and CKD risk factors associate with A) macro- anatomy findings of decreased renal cortical volume and focal scarring on CT scan among adults undergoing a standardized evaluation for potential kidney donation (n=4300), and B) micro-anatomy findings of nephrosclerosis and nephron size on renal biopsy among adults who actually donate a kidney (n=2500), and furthermore, to determine if increased nephron endowment is protective against age-related nephrosclerosis and the increased size of viable nephrons. Aim 2. To test the hypothesis that 10 novel serum and urine biomarkers for CKD (e.g., kidney injury molecule 1) associate with age-related changes A) in decreased renal cortical volume and focal scarring by CT scan (1500 potential donors) and B) in nephrosclerosis and nephron size by renal biopsy (1000 actual donors).

描述（申请人提供）：慢性肾脏病（CKD）既有临床描述（肾功能和尿液中蛋白质下降）又有病理描述（以肾小球硬化、肾小管萎缩、间质纤维化和动脉硬化为特征的肾硬化）。两者都随着年龄的增长而发生，但人们对它们之间的关系知之甚少。本研究的目标是描述两个地点（梅奥诊所和克利夫兰诊所）活体肾脏捐赠者大样本中肾脏与年龄相关的变化，以确定预测这些变化的生物标志物，并最终将肾脏病理学和生物标志物联系起来在未来的研究中检测肾脏病理和临床结果。结合计算机断层扫描 (CT) 扫描结果（肾皮质总体积）和肾活检结果（每肾皮质单位体积的肾小球）可以估计肾单位禀赋（一个人出生时就有的肾单位总数）。我们的中心假设是，随着衰老，进行性肾硬化会导致肾单位萎缩，并伴有皮质体积减少和疤痕。这种体积损失最初是通过活肾单位肥大来补偿的，这会导致进一步的肾硬化。然而，最终，肾硬化导致的体积损失压倒了剩余肾单位的代偿性肥大，肾脏体积缩小。目标 1. 检验以下假设：年龄、GFR、尿白蛋白和 CKD 危险因素与以下因素相关：A) 在接受潜在肾脏捐献标准化评估的成人中，肾皮质体积减少和 CT 扫描局灶性疤痕的宏观解剖学发现（n =4300），以及 B）实际捐献肾脏的成年人（n = 2500）中肾活检肾硬化和肾单位大小的显微解剖结果，此外，确定是否肾单位禀赋增加可以预防与年龄相关的肾硬化和存活肾单位大小的增加。目标 2. 检验以下假设：10 种新的 CKD 血清和尿液生物标志物（例如肾损伤分子 1）与年龄相关的变化相关：A) 通过 CT 扫描发现肾皮质体积减少和局灶性疤痕（1500 名潜在供体），B ) 通过肾活检了解肾硬化和肾单位大小（1000 名实际捐献者）。