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

描述（由申请人提供）：本申请是对PA-09-166“衰老中的肾功能和慢性肾脏疾病（CKD） （R21）”的响应。慢性肾病是老龄化人口中日益严重的问题。根据美国肾脏数据系统，终末期肾病（ESRD）老年患者的数量在过去25年中几乎翻了一番。因此，慢性肾病带来了相当大的医疗和公共卫生挑战，特别是在老年人群中。CKD是由肾小球滤过率（GFR）下降定义的肾功能下降。在大约70%的成年人中，GFR在40岁之前似乎是稳定的，然后以每十年8-10 mL/min的平均速度下降。肾功能的下降在病理上也表现为肾小管萎缩、肾小球硬化和间质纤维化。肾脏血管系统和血管功能的改变也可能导致CKD的发生。更好地了解CKD的病因和病理生理无疑将导致CKD的诊断和干预方法的改进。因此，NIH正在特别征求申请，以调查CKD与肾脏形态、病理、结构（如小管萎缩、肾小球硬化、间质纤维化）的年龄相关变化的关系。

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.