CKDdb-logoCKDdb - Study ID Exp25191961d

PubMed ID25191961
AuthorsWei Q, Xiao X, Fogle P, Dong Z.
TitleChanges in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion.
JournalPLoS One. 2014 Sep 5;9(9):e106647.
AbstractChanges of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseDetection method
Mus musculuskidneymedullaIRIGC/MS and LC/MS

Sample description and preparation

Disease (case)ischemia/reperfusion injury
Disease (control)healthy, sham operation
Disease inductionpedicles clamped (25 min of bilateral renal ischemia) + 2 hrs reperfusion
Preparation specific methodMetabolon's standard solvent extraction

Molecule list

Molecule IDextExternal IDNameRegulation (case/control)Scores
Z6798X17596inosineratio: 0.66p-value: < 0.05
Z6816 16708adenineratio: 0.52p-value: < 0.05
Z6799 16750guanosineratio: 0.46p-value: 0.05
Z6773 17361cytidine 5'-monophosphate (5'-CMP)ratio: 2.18p-value: < 0.05
Z5189 17802pseudouridineratio: 1.38p-value: < 0.05
Z4138 17924sorbitolratio: 0.18p-value: < 0.05
Z6390X15891taurineratio: 0.61p-value: < 0.05
Z4441 16899mannitolratio: 0.43p-value: < 0.05
Z531U 42090threitolratio: 0.65p-value: < 0.05

Compile date 08-10-2018© iMODE-CKD consortium