PharmacoPhotonics (FAST Diagnostics), LLC proposes research to extend the Phase I STTR 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, there is 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, FAST is developing and characterizing an optical measurement technique utilizing a novel minimally invasive Ratiometric Fluorescence Device (RFD) that can rapidly, accurately, and repetitively quantify the GFR, independent of serum or urinary measurements. FAST intends to more thoroughly characterize this approach using multi-photon microscopy and their 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. FAST will also initiate the development of a noninvasive device and marker molecules. Therefore, the purpose of this Phase II STTR project is to characterize the RFD in rats and then dogs, both under physiologic and AKI conditions, utilizing data on molecular markers gained in the Phase I study. FAST will then extend these observations into animal models of AKI including ischemia, sepsis, and nephrotoxins, such as aminoglycosides and radiocontrast agents. These studies will set the foundation for use of the RFD in human studies and further development of an initial noninvasive optical detection apparatus.

Public Health Relevance

Acute Kidney Injury (AKI) is a major and rapidly increasing cause of morbidity and mortality in hospitalized patients. Unfortunately, there is at present no diagnostic method to either rapidly diagnose and or quantify the extent of AKI, both of which are known to be important in the prognosis and treatment. FAST Diagnostics has developed a ratiometric fluorescent device and an associated technique allowing for rapid quantification of kidney function during AKI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
2R42DK079477-02
Application #
7669836
Study Section
Special Emphasis Panel (ZRG1-RUS-C (12))
Program Officer
Moxey-Mims, Marva M
Project Start
2008-06-10
Project End
2011-05-31
Budget Start
2009-07-10
Budget End
2010-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$589,241
Indirect Cost
Name
Pharmacophotonics, Inc.
Department
Type
DUNS #
787934012
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Molitoris, Bruce A (2017) Rethinking CKD Evaluation: Should We Be Quantifying Basal or Stimulated GFR to Maximize Precision and Sensitivity? Am J Kidney Dis 69:675-683
Von Hendy-Willson, Vanessa E; Pressler, Barrak M (2011) An overview of glomerular filtration rate testing in dogs and cats. Vet J 188:156-65