Renal disease is difficult to detect, particularly in a form called acute renal failure. We are developing new methods to detect renal disease involving either MRI, or urine or blood tests. 1)Detection of proximal tubule damage in mice MRI using dendrimer gadolinium chelate nanoparticles. We found that Gadolinium nanoparticles accumulate in the proximal tubule, and can be used to detect renal structure, function, and injury. We have now used these methods for the early detection and outcome prediction of sepsis-acute renal failure. This method can also be used as an intermediate surrogate biomarker that tracks therapy in sepsis-induced ARF. 2) Markers for early diagnosis. We are new using proteomic techniques to search for early biomarkers of sepsis-induced acute renal failure. We have a few excellent candidates that are being validated using our mouse and rat sepsis-acute renal failure models. 3) We have worked out the collection, storage, and processing conditions to use urinary exosomal proteins as biomarkers of renal disease. We are begining to serach for exosomal markers of structural renal injury in our animal models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK043400-06
Application #
7152645
Study Section
(MDB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Doi, Kent; Yuen, Peter S T; Eisner, Christoph et al. (2009) Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 20:1217-21
Zhou, Hua; Cheruvanky, Anita; Hu, Xuzhen et al. (2008) Urinary exosomal transcription factors, a new class of biomarkers for renal disease. Kidney Int 74:613-21
Bennett, Kevin M; Zhou, Hua; Sumner, James P et al. (2008) MRI of the basement membrane using charged nanoparticles as contrast agents. Magn Reson Med 60:564-74
Dear, J W; Yuen, P S T (2008) Setting the stage for acute-on-chronic kidney injury. Kidney Int 74:7-9
Dear, James W; Leelahavanichkul, Asada; Aponte, Angel et al. (2007) Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure. Crit Care Med 35:2319-28
Cheruvanky, Anita; Zhou, Hua; Pisitkun, Trairak et al. (2007) Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol 292:F1657-61
Zhou, Hua; Hewitt, Stephen M; Yuen, Peter S T et al. (2006) Acute Kidney Injury Biomarkers - Needs, Present Status, and Future Promise. Nephrol Self Assess Program 5:63-71
Zhou, H; Yuen, P S T; Pisitkun, T et al. (2006) Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int 69:1471-6
Holly, M K; Dear, J W; Hu, X et al. (2006) Biomarker and drug-target discovery using proteomics in a new rat model of sepsis-induced acute renal failure. Kidney Int 70:496-506
Zhou, H; Pisitkun, T; Aponte, A et al. (2006) Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int 70:1847-57

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