1) Continuing our work on exosomes as a source of biomarkers, we found that transcription factors ATF3 and WT-1 were capable of detecting acute kidney injury and chronic kidney disease, respectively, in animal models and a few patients. We continue refinement of these promising biomarker candidates in larger sets of patients, as well as in animal models.? ? 2) We have shifted our MRI imaging efforts from gadolinium-based contrast agents, whose potential for toxicity impedes further development, to less toxic agents. We were used a novel contrast agent, cationized ferritin, designed to be retained by the glomerular basement membrane, as a contrast agent to detect glomeruli. By MRI with cationized ferritin normal rats could be distinguished from rats with focal segmental glomerulosclerosis, where the glomerular basement membrane is disrupted.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2008
Total Cost
$588,468
Indirect Cost
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
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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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