TY - JOUR
T1 - Unique transcriptional programs identify subtypes of AKI
AU - Xu, Katherine
AU - Rosenstiel, Paul
AU - Paragas, Neal
AU - Hinze, Christian
AU - Gao, Xiaobo
AU - Shen, Tian Huai
AU - Werth, Max
AU - Forster, Catherine
AU - Deng, Rong
AU - Bruck, Efrat
AU - Boles, Roger W.
AU - Tornato, Alexandra
AU - Gopal, Tejashree
AU - Jones, Madison
AU - Konig, Justin
AU - Stauber, Jacob
AU - D'Agati, Vivette
AU - Erdjument-Bromage, Hediye
AU - Saggi, Subodh
AU - Wagener, Gebhard
AU - Schmidt-Ott, Kai M.
AU - Tatonetti, Nicholas
AU - Tempst, Paul
AU - Oliver, Juan A.
AU - Guarnieri, Paolo
AU - Barasch, Jonathan
N1 - Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017/6
Y1 - 2017/6
N2 - Two metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to theinjuryof thekidney tubuleandtheepithelial cells thereof (AKI).Yetneither criterionemphasizes theetiology 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 lasermicrodissection to isolate specific domains of the kidney, followed by RNAsequencing,we found that thousands of genes responded specifically to iAKI or to vAKI, but very fewresponded 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 potentialbiomarkers 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.
AB - Two metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to theinjuryof thekidney tubuleandtheepithelial cells thereof (AKI).Yetneither criterionemphasizes theetiology 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 lasermicrodissection to isolate specific domains of the kidney, followed by RNAsequencing,we found that thousands of genes responded specifically to iAKI or to vAKI, but very fewresponded 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 potentialbiomarkers 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.
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U2 - 10.1681/ASN.2016090974
DO - 10.1681/ASN.2016090974
M3 - Article
C2 - 28028135
AN - SCOPUS:85021633767
SN - 1046-6673
VL - 28
SP - 1729
EP - 1740
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 6
ER -