Non-Invasive Optical Determination of GFR

描述(由申请人提供)：Pharmaco Photonics，LLC提出了一种新的双光子体内荧光方法来监测急性肾损伤(AKI)的肾小球滤过率(GFR)的研究。AKI仍然是一个令人头疼的临床问题，导致患者死亡率高得令人无法接受，发展成慢性肾脏疾病，并加速进展为终末期肾脏疾病。尽管发生AKI的临床风险因素已经确定，但我们没有合理的监测技术(“生物标记物”)来明确和快速地诊断或确定任何患者的AKI的严重程度。由于患者的预后与损伤的程度相关，而有效的治疗需要早期干预，因此快速诊断患者并根据患者的肾脏损伤程度对患者进行分层的能力对这一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)，而不依赖于血或尿的测量。我们的意图是使用多光子显微镜和我们的专利比率技术更彻底地表征这种方法，该技术使用了两个荧光报告分子。这种定量比率光学方法最大限度地减少了强度荧光测定的固有限制，并允许快速准确地测定GFR。这个第一阶段STTR项目的目的是确定在组成和分子大小方面的最佳候选分子，用于量化GFR，同时将候选分子的非肾脏清除降至最低。然后，我们将把这些观察扩展到急性肾损伤的动物模型中，包括缺血、脓毒症和肾毒素，如氨基糖苷类和放射造影剂。这些研究将为我们在第二阶段应用中开发我们的非侵入性光学检测设备奠定基础。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，死亡率很高。目前还没有快速检测或确定损伤严重程度的诊断试验。这限制了有效测试潜在新疗法的能力。Pharmaco Photonics，LLC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.