Unique Transcriptional Programs Identify Subtypes of AKI.

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.

DOI: 10.1681/ASN.2016090974

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@article{Xu2017UniqueTP, title={Unique Transcriptional Programs Identify Subtypes of AKI.}, author={Katherine Xu and Paul E. Rosenstiel and Neal A Paragas and Christian Hinze and Xiaobo Gao and Tian Huai Shen and Max Werth and Catherine S Forster and Rong Deng and Efrat Bruck and Roger W Boles and Alexandra Tornato and Tejashree Gopal and Madison Jones and Justin Konig and Jacob Stauber and Vivette D D'agati and Hediye Erdjument-Bromage and Subodh J. Saggi and Gebhard Wagener and Kai M. Schmidt-Ott and Nicholas Tatonetti and Paul Tempst and Juan Oliver and Paolo Guarnieri and Jonathan Barasch}, journal={Journal of the American Society of Nephrology : JASN}, year={2017}, volume={28 6}, pages={1729-1740} }