Non-Invasive Optical Determination of GFR

Molitoris, Bruce

Abstract

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. ? ? ?