CHRONIC KIDNEY INJURY FROM ENDOTHELIAL DYSFUNCTION AFTER ACUTE KIDNEY INJURY

急性肾损伤后内皮功能障碍导致的慢性肾损伤

• 批准号: 7603252
• 负责人: DAVID J ASKENAZI
• 金额: $ 0.47万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603252
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Age; Animal Model; Biological Markers; Bladder; Blood Pressure; Cardiac; Cardiovascular system; Child; Chronic; Chronic Kidney Failure; Cimetidine; Clinic Visits; Collection; Computer Retrieval of Information on Scientific Projects Database; Creatinine; Creatinine clearance measurement; Endothelial Cells; Endothelium; Event; Factor VIII-Related Antigen; Functional disorder; Funding; Grant; Health; Hour; Hypertension; Injury; Institution; Kidney; Lead; Measures; Meat; Methods; Microalbuminuria; Morbidity - disease rate; Outcome; Patients; Process; Proteins; Proteomics; Renal Tissue; Renal function; Research; Research Personnel; Resources; Series; Serum; Source; Techniques; Therapeutic Intervention; Time; Tubular formation; Ultrasonography; United States National Institutes of Health; Urine; VWF gene; Vascular Endothelial Cell; Visit; day; glomerular function; kidney vascular structure; mortality; sex; urinary; von Willebrand Factor

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. Background. After an ischemic acute kidney injury (AKI) event, tubular and glomerular function usually return to baseline, but growing evidence in animal models shows that damage occurring to the innermost layer of the renal vasculature (endothelial cells) can propagate a series of events that cause progressive renal injury. Endothelial damage has been show to independently predict poor cardiovascular health in cardiac and renal patients. Not much is know about the mechanisms involved in this process that begins with AKI and culminates in chronic renal disease. Children who develop AKI are an ideal group to study because the timing of initiation of events is known and they are less likely to have co-morbid illness. Therapeutic interventions to halt this progression can greatly reduce the morbidity and mortality associated with AKI. Hvpothesis and Aims: After AKI, most chil dren regain the majority of their renal function but the damage to renal vascular endothelial cells occurs which initiates events that lead to CKD and poor cardiovascular health. AIM 1: One month after AKI, children have less renal function reserve (RFR) compared to controls. AIM 2: One year after event, children with AKI have worsening RFR compared to controls. AIM 3: After AKI children with decreased RFR have elevated endothelial biomarkers. Proteomic techniques will discover new urinary biomarkers that occur in this setting. Methods: 20 otherwise healthy children with AKI and 20 age and sex matched controls will have blood pressure, serum and urine analysis on 2 separate clinic visits 9 months apart. Because 20-25% of existing renal tissue needs to be damaged prior to seeing change in GFR, RFR will be our primary outcome as it is more specific for renal injury. Briefly, RFR is performed as follows: Children will be on cimetidine for 2 days to block tubular secretion of creatinine. First, a baseline GFR will be measured by a 2-hour creatinine clearance (this method has previously b en validated as an adequate measure of GFR). Next, a 1 g/kg of non-meat protein meal challenge will be given prior to a second 2-hour reatinine clearance. RFR is the difference between baseline GFR and protein challenged GFR. Bladder ultrasound will confirm complete emptying before and after collection. AIM I: Compare RFR between those with recent AKI and controls. AIM 2: Compare the 9 month difference in RFR between the two groups. AIM 3: At both visits known biomarkers of endothelium damage will be measured and compared between the groups. These include microalbuminuria, hypertension, and serum biomarkers (hs-CRP, vWF,). Urine proteomic techniques will be performed to investigate for potential urine biomarkers present in children after AKI.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 背景。经过缺血性急性肾脏损伤（AKI）事件后，管状和肾小球功能通常恢复到基线，但动物模型中越来越多的证据表明，肾脏脉管系统（内皮细胞）最内层的损害可能导致一系列事件，这些事件会导致一系列事件，这些事件会导致一系列事件 进行性肾脏损伤。表明内皮损害可以独立预测心血管和肾脏患者的心血管健康状况不佳。对此过程涉及的机制知之甚少，该过程始于AKI，并在慢性肾脏疾病中达到顶峰。发展AKI的孩子是一个理想的学习群体，因为已知事件的开始时间，并且不太可能患有疾病。阻止这种进展的治疗干预措施可以大大降低与AKI相关的发病率和死亡率。 HVPothesis和目标：在AKI之后，大多数Chil Dren恢复了其大部分肾功能，但肾脏血管内皮细胞的损害发生了，这会引发导致CKD和不良心血管健康的事件。 AIM 1：AKI后一个月，与对照组相比，儿童的肾功能储备（RFR）较少。 AIM 2：事件发生后一年，与对照组相比，AKI的儿童将恶化RFR恶化。 AIM 3：AKI患有RFR降低的儿童具有升高的内皮生物标志物。蛋白质组学技术将发现在这种情况下发生的新泌尿生物标志物。 方法：20个具有AKI和20岁和性匹配的对照的健康儿童将在2个单独的诊所就诊时进行血压，血清和尿液分析。由于20-25％的现有肾组织需要在看到GFR发生变化之前受到损坏，因此RFR将是我们的主要结果，因为它更特定于肾脏损伤。简而言之，RFR的进行如下：儿童将在西米丁氨酸上2天，以阻止肌酐的管状分泌。首先，将通过2小时的肌酐​​清除率测量基线GFR（此方法先前已被证明为足够的衡量标准 GFR）。接下来，在第二个2小时的重氨酸清除率之前，将提出1 g/kg的非糖蛋白粉挑战。 RFR是基线GFR和蛋白质挑战GFR之间的差异。膀胱超声将确认收集前后的清空。 AIM I：将RFR与最近的AKI和控件进行比较。 AIM 2：比较两组之间RFR的9个月差异。 AIM 3：两组之间将测量并比较两次访问的已知内皮损伤生物标志物。这些包括微量白蛋白尿，高血压和血清生物标志物（HS-CRP，VWF，）。将进行尿液蛋白质组学技术，以调查AKI后儿童中存在的潜在尿液生物标志物。