1) Most of our efforts have been focused on exosomes as a source of biomarkers. Typically, exosomes are isolated from urine by differential centrifugation, including an ultracentrifugation step. We developed a simpler procedure to isolate urinary exosomes? by using a nanomembrane ultrafiltration concentrator that allows low speed centrifugation to replace the ultracentrifugation step. This should facilitate the discovery and validation of exosomal biomarkers, especially in laboratories that do not have access to an ultracentrifuge.? ? 2) Expanding our search for biomarkers, we used proteomic discovery methods to examine the liver during early and later stages of sepsis. As liver injury precedes kidney injury, and our data suggest that there may be passive and/or active communication between organs, we sought liver proteins that could predict and/or mediate kidney injury. We validated the most promising candidates by western blot, and were able to demonstrate the functional significance of one candidate, cyclophilin A, by using an antibody against its receptor CD147.? ? 3) Markers for early diagnosis. We continue to use microarray and proteomic techniques to search for early biomarkers of ischemia/reperfusion-, nephrotoxic-, and sepsis-induced acute kidney injury. We have a few excellent candidates, including Fetuin A, that are being validated using our mouse and rat acute kidney injury models, as well as in AKI patients.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2007
Total Cost
$414,624
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
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, 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
Riss, Joseph; Khanna, Chand; Koo, Seongjoon et al. (2006) Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma. Cancer Res 66:7216-24
Dear, James W; Kobayashi, Hisataka; Brechbiel, Martin W et al. (2006) Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents. Nephron Clin Pract 103:c45-9
Yuen, Peter S T; Jo, Sang-Kyung; Holly, Mikaela K et al. (2006) Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses. Physiol Genomics 25:375-86

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