AGE-RELATED CHANGES IN RENAL MORPHOLOGY AND FUNCTION IN CHRONIC KIDNEY DISEASE

慢性肾病中肾脏形态和功能与年龄相关的变化

• 批准号: 8517551
• 负责人: Yu Chen
• 金额: $ 21.91万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8517551
• 关键词: 2 year old; Adult; Age; Age-Years; Aging; Animal Model; Animals; Area; Atrophic; Biomedical Engineering; Biometry; Blood Vessels; Caliber; Chronic Kidney Failure; Collaborations; Confocal Microscopy; Contrast Media; Data; Data Set; Development; Diagnosis; End stage renal failure; Etiology; Fibrosis; Fluorescence; Functional disorder; Glomerular Filtration Rate; Healthcare; Human; Image; Information Systems; Intervention; Kidney; Lead; Location; Maryland; Measurement; Medical; Methods; Microcirculation; Molecular; Molecular and Cellular Biology; Monitor; Morphology; Older Population; Optical Coherence Tomography; Pathology; Patients; Physiology; Public Health; Quality of life; Rattus; Renal function; Research; Research Personnel; Resolution; Sampling; Staging; Statistical Data Interpretation; Structure; Technology; Testing; Texture; Time; Tissues; Tubular formation; United States; United States National Institutes of Health; Universities; age related; aging population; experience; glomerular filtration; glomerulosclerosis; hemodynamics; improved; in vivo; interstitial; kidney imaging; middle age; older patient; optical imaging; response; senescence; young adult

DESCRIPTION (provided by applicant): This application is in response to PA-09-166 "Renal Function and Chronic Kidney Disease (CKD) in Aging (R21)". CKD is a growing problem among the aging population. According to the United States Renal Data System, the number of older patients with end-stage renal disease (ESRD) has almost doubled over the last 25 years. Thus, CKD poses a considerable medical and public health challenge, particularly in the older population. CKD is a decline in renal function defined by decreased glomerular filtration rate (GFR). GFR appears to be stable until about 40 years of age and then declines at an average rate of 8-10 mL/min/per decade in approximately 70% of adults. The decline in renal function is also characterized pathologically by tubular atrophy, glomerulosclerosis, and interstitial fibrosis Alterations in renal vasculature and vascular function may also contribute to the development of CKD. A better understanding of the etiology and pathophysiology of CKD will undoubtedly lead to improved methods in both diagnosis and intervention of CKD. Therefore, NIH is specifically soliciting applications to investigate the "relationship of CKD to age-related changes in renal morphology, pathology, structure (e.g., tubular atrophy, glomerulosclerosis, interstitial fibrosis) and function (e.g., changes in renal hemodynamics, GFR, etc.)." We hypothesize that a multi-modal optical imaging platform combining optical coherence tomography (OCT) and fluorescence confocal microscopy (FCM) can: 1) provide quantitative measurements of structural and functional parameters in CKD; and 2) longitudinal monitor age-related changes in renal structure and function. Our extensive preliminary data on both animal and human kidneys demonstrate the strong potential and promise of optical imaging for evaluating kidney pathology and function in vivo. We propose to test our hypothesis on animal models by pursuing the following two specific aims: Aim 1: Quantitatively image animal model of CKD using combined OCT/FCM and correlate renal morphological and functional parameters with the progression of CKD. Specifically, we will quantify morphometric parameters from OCT; hemodynamic parameters from DOCT; and glomerular filtration parameters from FCM. Those parameters will be statistically analyzed to correlate with CKD. Aim 2: Quantitatively investigate the relationship between renal morphological and functional parameters with age-related progression of CKD on an animal model of aging. Specifically, we will longitudinally image four groups of animals: young adult rats (3-4 months), middle age (8-10 months), old rats (18 months), and senescent rats (22-24 months) and monitor the age-related progression of CKD. At each time point, optical imaging parameters will be sampled from multiple locations to attain a representative description of global kidney status. Furthermore, we will image multiple animals at each time point to statistically investigate the interplay between renal structural/functional parameters and age-related progression of CKD.

描述（由申请人提供）：本申请是对PA-09-166“老年人的肾功能和慢性肾病（CKD）（R21）"的回应。CKD是老龄化人口中日益严重的问题。根据美国肾脏数据系统，在过去25年中，患有终末期肾病（ESRD）的老年患者人数几乎翻了一番。因此，CKD构成了相当大的医疗和公共卫生挑战，特别是在老年人群中。CKD是肾功能下降，定义为肾小球滤过率（GFR）降低。GFR似乎在大约40岁之前保持稳定，然后在大约70%的成年人中以每十年8-10 mL/min的平均速率下降。肾功能下降的病理特征还包括肾小管萎缩、肾小球硬化和间质纤维化。肾血管系统和血管功能的改变也可能导致CKD的发展。更好地了解CKD的病因学和病理生理学无疑将导致CKD的诊断和干预方法的改进。因此，NIH特别征求申请，以调查“CKD与肾脏形态学、病理学、结构（例如，肾小管萎缩、肾小球硬化、间质纤维化） 和功能（例如，肾血流动力学、GFR等的变化）。“我们假设，结合光学相干断层扫描（OCT）和荧光共聚焦显微镜（FCM）的多模态光学成像平台可以：1）提供CKD结构和功能参数的定量测量; 2）纵向监测肾脏结构和功能的年龄相关变化。我们对动物和人类肾脏的大量初步数据表明，光学成像在体内评估肾脏病理和功能方面具有强大的潜力和前景。我们提出通过追求以下两个具体目标来测试我们的动物模型假设：目标1：使用组合OCT/FCM对CKD动物模型进行定量成像，并将肾脏形态学和功能参数与CKD的进展相关联。具体而言，我们将量化OCT的形态学参数; DOCT的血流动力学参数; FCM的肾小球滤过参数。将对这些参数进行统计学分析，以确定其与CKD的相关性。目的2：定量研究 肾脏形态和功能参数与年龄相关的CKD进展之间的关系。具体而言，我们将对四组动物进行纵向成像：年轻成年大鼠（3-4个月），中年大鼠（8-10个月），老年大鼠（18个月）和衰老大鼠（22-24个月），并监测与年龄相关的CKD进展。在每个时间点，将从多个位置采样光学成像参数，以获得总体肾脏状态的代表性描述。此外，我们将在每个时间点对多只动物进行成像，以统计学研究肾脏结构/功能参数之间的相互作用， CKD的年龄相关进展。

项目成果

Concurrent multiscale imaging with magnetic resonance imaging and optical coherence tomography.

磁共振成像和光学相干断层扫描的并行多尺度成像。

• DOI: 10.1117/1.jbo.18.4.040506
• 发表时间: 2013
• 期刊: Journal of biomedical optics
• 影响因子: 3.5
• 作者: Liang,Chia-Pin;Yang,Bo;Kim,IlKyoon;Makris,George;Desai,JaydevP;Gullapalli,RaoP;Chen,Yu
• 通讯作者: Chen,Yu