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Unique Transcriptional Programs Identify Subtypes of AKI.

Citation
Xu, K., et al. “Unique Transcriptional Programs Identify Subtypes Of Aki.”. Journal Of The American Society Of Nephrology : Jasn, pp. 1729-1740.
Center University of Washington
Author Katherine Xu, Paul Rosenstiel, Neal Paragas, Christian Hinze, Xiaobo Gao, Tian Huai Shen, Max Werth, Catherine Forster, Rong Deng, Efrat Bruck, Roger W Boles, Alexandra Tornato, Tejashree Gopal, Madison Jones, Justin Konig, Jacob Stauber, Vivette D'Agati, Hediye Erdjument-Bromage, Subodh Saggi, Gebhard Wagener, Kai M Schmidt-Ott, Nicholas Tatonetti, Paul Tempst, Juan A Oliver, Paolo Guarnieri, Jonathan Barasch
Keywords acute kidney injury, biomarkers, renal ischemia, transcriptional profiling, volume depletion
Abstract

Two metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to the injury of the kidney tubule and the epithelial cells thereof (AKI). Yet neither criterion emphasizes the etiology or the pathogenetic heterogeneity of acute decreases in kidney excretory function. In fact, whether decreased excretory function due to contraction of the extracellular fluid volume (vAKI) or due to intrinsic kidney injury (iAKI) actually share pathogenesis and should be aggregated in the same diagnostic group remains an open question. To examine this possibility, we created mouse models of iAKI and vAKI that induced a similar increase in serum creatinine concentration. Using laser microdissection to isolate specific domains of the kidney, followed by RNA sequencing, we found that thousands of genes responded specifically to iAKI or to vAKI, but very few responded to both stimuli. In fact, the activated gene sets comprised different, functionally unrelated signal transduction pathways and were expressed in different regions of the kidney. Moreover, we identified distinctive gene expression patterns in human urine as potential biomarkers of either iAKI or vAKI, but not both. Hence, iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify our current definitions of acute changes in kidney excretory function.

Year of Publication
2017
Journal
Journal of the American Society of Nephrology : JASN
Volume
28
Issue
6
Number of Pages
1729-1740
Date Published
06/2017
ISSN Number
1533-3450
DOI
10.1681/ASN.2016090974
Alternate Journal
J. Am. Soc. Nephrol.
PMID
28028135
PMCID
PMC5461802
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