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; 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）既有临床描述（尿液中的肾功能和蛋白质降低），也具有病理描述（肾脏骨硬化为特征，其特征是肾小球萎缩，间质纤维化，间质纤维化和动脉粥样硬化）。 两者都是随着年龄的增长而发生的，但对它们之间的关系知之甚少。 这项研究的目的是表征在两个部位（Mayo Clinic和Cleveland诊所）的大量活肾脏供体样本中，肾脏中与年龄相关的变化，以鉴定预测这些变化的生物标志物，并最终将检测肾脏病理学的肾脏病理学和生物标志物与未来研究中的临床表现相关。 结合计算机断层扫描（CT）扫描发现（总肾皮质体积）和肾脏活检结果（每个肾脏皮层单位量）允许估计肾脏end赋（一个人诞生的肾单位总数）。我们的中心假设是，随着衰老，进行性肾脏硬化的衰老，会导致肾脏萎缩，具有皮质体积损失和疤痕。 该体积损失最初是通过可行肾脏的肥大来补偿的，这导致进一步的肾细胞化。 然而，最终，肾脏严重的体积损失淹没了剩余肾脏的补偿性肥大，肾脏的大小降低。 目的1。要测试以下假说：年龄，GFR，尿白蛋白和CKD风险因素与a）与肾脏皮质量减少和对CT扫描的宏观解剖结构相关的发现，并在接受潜在肾脏捐赠的标准化评估的成年人中扫描（n = 4300）的标准化评估（n = 4300），以及微型生物宣传型培训，以及bry-nephrron sie whorron和nephrron，and和neperron的肾脏介绍。捐赠肾脏（n = 2500），此外，以确定肾脏捐赠的增加是否可以抵抗与年龄相关的肾脏症和可行肾脏的大小增加。 目的2。为了测试CKD的10种新型血清和尿液生物标志物（例如肾脏损伤分子1）与年龄相关的变化a）在肾脏病（1500个潜在的供体）中减少肾脏皮质体积和局灶性疤痕（肾小球病和b）在肾小球病和肾脏尺寸中，由肾脏尺寸划分为肾脏brebersy（肾小管）。 公共卫生相关性：随着成年人的年龄，肾脏中的某些健康组织逐渐被疤痕组织取代。 我们计划确定临床测试是否可以检测到肾脏中与年龄相关的变化。 这将提高我们对慢性肾脏疾病随着年龄的增长的方式的理解，并最终导致更好的诊断，预防和治疗慢性肾脏疾病的方法。