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

• 批准号: 8022523
• 负责人: ANDREW David RULE
• 金额: $ 70.65万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 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/8022523
• 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; rat KIM-1 protein; renal artery; renal scarring; response

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). PUBLIC HEALTH RELEVANCE: As adults age, some of the healthy tissue in the kidney is gradually replaced by scar tissue. We plan to determine whether clinical tests can detect these age-related changes in the kidney. This will improve our understanding of how chronic kidney disease develops in people as they age and eventually lead to better ways to diagnose, prevent, and treat chronic kidney disease.

描述（由申请人提供）：慢性肾脏疾病（CKD）有临床描述（肾功能降低和尿蛋白减少）和病理描述（肾硬化，特征为肾小球硬化、肾小管萎缩、间质纤维化和动脉硬化）。 两者都随着年龄的增长而发生，但对它们之间的关系知之甚少。 本研究的目的是在两个研究中心（马约诊所和克利夫兰诊所）的大样本活体肾脏供体中表征年龄相关的肾脏变化，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检测肾脏病理学的生物标志物与未来研究的临床结局联系起来。 结合计算机断层扫描（CT）扫描结果（总肾皮质体积）和肾活检结果（肾小球/肾皮质单位体积），可以估计肾单位禀赋（一个人出生时的肾单位总数）。我们的中心假设是，随着年龄的增长，进行性肾硬化导致肾单位萎缩，皮质体积减少和瘢痕形成。 这种体积损失最初由存活肾单位的肥大补偿，这导致进一步的肾硬化。 然而，最终，肾硬化引起的体积损失会使剩余肾单位代偿性肥大，肾脏体积缩小。 目标1.为了检验年龄、GFR、尿白蛋白和CKD风险因素与以下因素相关的假设：A）接受标准化评价潜在肾脏捐献的成人（n=4300）中CT扫描显示的肾皮质体积减小和局灶性瘢痕的宏观解剖学结果，和B）实际捐献肾脏的成人（n=2500）中肾活检显示的肾硬化和肾单位大小的微观解剖学结果。此外，确定增加的肾单位禀赋是否对年龄相关的肾硬化和存活肾单位的大小增加具有保护作用。 目标2.为了检验10种新的CKD血清和尿液生物标志物（例如，肾损伤分子1）与年龄相关变化相关，A）通过CT扫描（1500名潜在供体）肾皮质体积减小和局灶性瘢痕形成，和B）通过肾活检（1000名实际供体）肾硬化和肾单位大小。 公共卫生相关性：随着成年人年龄的增长，肾脏中的一些健康组织逐渐被疤痕组织所取代。 我们计划确定临床测试是否可以检测到这些与年龄相关的肾脏变化。 这将提高我们对慢性肾脏疾病如何随着年龄的增长而发展的理解，并最终导致更好的诊断，预防和治疗慢性肾脏疾病的方法。