Non-Invasive Optical Determination of GFR

GFR 的无创光学测定

• 批准号: 7480616
• 负责人: Bruce A Molitoris
• 金额: $ 10.37万
• 依托单位: PHARMACOPHOTONICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-10 至 2009-06-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480616
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Aminoglycosides; Animal Disease Models; Animal Model; Biological Markers; Blood; Blood Vessels; Cardiac; Chronic; Chronic Kidney Failure; Clinical; Condition; Creatinine; Detection; Development; Diagnosis; Diagnostic tests; Early Intervention; Elderly; End stage renal failure; Equation; Equilibrium; Etiology; Fluorescence; Foundations; Glomerular Filtration Rate; Healthcare; Human; Image; Indiana; Injury; Intention; Invasive; Ischemia; Kidney; Kidney Diseases; Label; Lasers; Legal patent; Licensing; Light; Liver diseases; Maintenance; Measurement; Measures; Medical Surveillance; Methods; Microscopy; Modeling; Molecular; Molecular Weight; Monitor; Multiple Trauma; Numbers; Optics; Outcome; Patient Care; Patients; Phase; Phase II Clinical Trials; Photons; Physiological; Plasma; Population; Procedures; Protein Binding; Public Health; Purpose; Radioactivity; Rate; Recovery; Renal clearance function; Renal function; Reporter; Research; Risk; Risk Factors; Scanning; Sepsis; Serum; Severities; Signal Transduction; Small Business Technology Transfer Research; Source; Staging; Standards of Weights and Measures; Stream; System; Techniques; Technology; Testing; Time; Tube; Universities; base; care burden; detector; diabetic; immunogenic; in vivo; molecular size; mortality; multi-photon; novel; optical fiber; rapid detection; success; two-photon; urinary

DESCRIPTION (provided by applicant): PharmacoPhotonics, LLC proposes research leading to a novel 2-photon in vivo fluorescence method for monitoring glomerular filtration rate (GFR) in acute kidney injury (AKI). AKI remains a vexing clinical problem resulting in unacceptably high patient mortality, development of chronic kidney disease and enhanced progression to end stage renal disease. Although clinical risks factors for developing AKI have been identified, we have no reasonable surveillance technique ("biomarker") to definitively and rapidly diagnose or determine the extent of severity of AKI in any patient. Since patient outcomes correlate with the extent of injury, and effective therapy requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for clinical progress in this field. Therefore, we are developing and characterizing an optical measurement technique that can rapidly, accurately and repetitively quantify the glomerular filtration rate (GFR) independent of serum or urinary measurements. It is our intention to more thoroughly characterize this approach using multi-photon microscopy and our patented ratiometric technique utilizing two fluorescent reporter molecules. This quantitative ratiometric optical approach minimizes the inherent limitations of intensity fluorescence determinations and allows for rapid and accurate determination of GFR. The purpose of this Phase 1 STTR project is to identify the best molecular candidate, both in composition and molecular size, to be used for quantifying GFR and at the same time minimizing non-renal clearance of candidate molecules. We will then extend these observations into animal models of acute kidney injury including ischemia, sepsis, and nephrotoxins such as aminoglycosides and radiocontrast agents. These studies will set the foundation for development of our noninvasive optical detection apparatus in a Phase 2 application. PUBLIC HEALTH RELEVANCE Acute kidney injury remains a major health care burden with a high mortality rate. At the present time there is no diagnostic test for rapid detection or determination of the severity of injury. This has limited the ability to effectively test potential new therapies. PharmacoPhotonics, LLC is developing a non-invasive optical technique to meet this need.

描述（由申请人提供）：PharmacoPhotonics，LLC提出了一种新型双光子体内荧光方法，用于监测急性肾损伤（阿基）中的肾小球滤过率（GFR）。阿基仍然是一个令人烦恼的临床问题，导致不可接受的高患者死亡率、慢性肾病的发展和向终末期肾病的加速进展。虽然已经确定了发生阿基的临床风险因素，但我们没有合理的监测技术（“生物标志物”）来明确和快速诊断或确定任何患者的阿基严重程度。由于患者的预后与损伤程度相关，有效的治疗需要早期干预，因此根据肾损伤程度快速诊断和分层患者的能力对于该领域的临床进展至关重要。因此，我们正在开发和表征一种光学测量技术，该技术可以快速，准确和重复地量化肾小球滤过率（GFR），而不依赖于血清或尿液测量。这是我们的意图，更彻底地表征这种方法使用多光子显微镜和我们的专利比率技术，利用两个荧光报告分子。这种定量比率光学方法最大限度地减少了荧光强度测定的固有局限性，并允许快速准确地测定GFR。该I期STTR项目的目的是确定组成和分子大小方面的最佳候选分子，用于定量GFR，同时最大限度地减少候选分子的非肾脏清除。然后，我们将这些观察扩展到急性肾损伤的动物模型，包括缺血，脓毒症，肾毒素，如氨基糖苷类和放射性造影剂。这些研究将为我们的非侵入性光学检测设备在第二阶段的应用奠定基础。公共卫生相关性急性肾损伤仍然是一个主要的卫生保健负担，死亡率高。目前还没有快速检测或确定损伤严重程度的诊断测试。这限制了有效测试潜在新疗法的能力。PharmacoPhotonics，LLC正在开发一种非侵入性光学技术来满足这一需求。