Non-Invasive Optical Determination of GFR

描述（由申请人提供）：PharmacoPhotonics， LLC提议研究一种新的2光子体内荧光方法，用于监测急性肾损伤（AKI）的肾小球滤过率（GFR）。AKI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，慢性肾脏疾病的发展和加速进展到终末期肾脏疾病。虽然已经确定了发生AKI的临床危险因素，但我们没有合理的监测技术（“生物标志物”）来明确和快速地诊断或确定任何患者的AKI严重程度。由于患者的预后与损伤程度相关，而有效的治疗需要早期干预，因此根据患者的肾损伤程度快速诊断和分层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，可以快速，准确和重复量化肾小球滤过率（GFR）独立于血清或尿液测量。我们打算使用多光子显微镜和我们的专利比例技术，利用两个荧光报告分子，更彻底地表征这种方法。这种定量比例光学方法最大限度地减少了强度荧光测定的固有局限性，并允许快速准确地测定GFR。本1期STTR项目的目的是确定最佳候选分子，包括组成和分子大小，用于量化GFR，同时最大限度地减少候选分子的非肾清除率。然后，我们将这些观察结果扩展到急性肾损伤的动物模型中，包括缺血、败血症和肾毒素，如氨基糖苷类和放射造影剂。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。急性肾损伤仍然是死亡率高的主要卫生保健负担。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有限责任公司正在开发一种非侵入性光学技术来满足这一需求。

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.