Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
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Review

Volume 15, Number 6, June 2023, pages 283-291

Metabolomics in Acute Kidney Injury: The Experimental Perspective

Figure

Figure 1.
Figure 1. Metabolomics-derived findings in experimental AKI. Ischemia induces multiple deteriorations of lipid, glucose, and energy metabolism. In addition, the complement activity increases, coagulation pathways are activated, and prostaglandin synthesis is stimulated. These events, in conjunction, induce and perpetuate tubular cell dysfunction/damage, interstitial inflammation, and microvasculopathy. Under experimental conditions, both LPS and cisplatin also impair lipid and energy metabolism. Cisplatin particularly modulates the tryptophan pathway, most likely a key mechanism in cisplatin-induced AKI. LPS: lipopolysaccharide; AKI: acute kidney injury; ATP: adenosine triphosphate.

Table

Table 1. Summary of All Experimental Studies Discussed in the Text
 
ReferenceDesignOutcome/conclusion
CPB/DHCA: cardiopulmonary bypass including so-called deep hypothermic circulatory arrest; AKI: acute kidney injury; ATP: adenosine triphosphate; LPS: lipopolysaccharide.
Ischemic AKI
  Liu et al, 2012 [42]Bilateral renal ischemia (45 min) in Sprague-Dawley rats, L-carnitine pretreatment in one groupIncrease of serum lysophospholipids and free fatty acids, decreased activity of serum phospholipase A2/ischemia-associated dysregulation of lipid metabolism
  Wei et al, 2014 [44]Bilateral renal ischemia in mice (25 min), analyzes at 2 or 48 h or at 7 days after reperfusionAlterations in glucose, lipid, and purine metabolism/identification of candidates involved in energy depletion and inflammation
  Huang et al, 2018 [45]Unilateral renal ischemia in rats (45 min)Increased availability of stress signaling proteins (proteomics analysis), increase of cortical lipid metabolites, accompanied by lower tissue glucose levels
  Fox et al, 2019 [46]Experimental cardiorenal syndrome type 3 (6) in mice (bilateral renal ischemia for 22 min)Intrarenal amino acid depletion and oxidative stress, intracardiac stimulation of anaerobic ATP synthesis/experimental confirmation of reno-cardiac cross-talk in AKI
  Davidson et al, 2022 [49]Cardiopulmonary bypass including so-called deep hypothermic circulatory arrest (CPB/DHCA) in pigletsStimulated anaerobic glycolysis in AKI piglets/anaerobic glycolysis as potential biomarker of early AKI in CPB
Toxic AKI
  Izquierdo-Garcia et al, 2019 [52]Living Escherichia coli for sepsis induction in pigsMultiple metabolic abnormalities in kidney tissue, serum, and urine, correlations between certain urine metabolites and established AKI biomarkers/metabolomics help to identify novel AKI biomarker molecules
  Qu et al, 2020 [53]Intraperitoneal cisplatin injections (Sprague-Dawley rats), urine and renal tissue analyzesDysregulation of tissue amino acid and lipid metabolism; additional identification of AKI biomarker candidates in urine samples
  Gao et al, 2021 [54]LPS-induced multiorgan failure in ratsSignificant tissue damage in liver, lungs, colon, and kidney, alteration of more than 50 metabolic pathways upon LPS administration/conclusion rather vague
  Ping et al, 2021 [55]LPS treatment of Sprague-Dawley ratsStimulation of aerobic and anaerobic metabolism, impaired oxygen supply, abnormalities in fatty acid metabolism/alterations proposed as key events in sepsis-associated AKI
  Tan et al, 2021 [56]Cisplatin-induced AKI in Sprague-Dawley rats, targeted analysis of the tryptophan metabolismIdentification of indoxyl sulfate as key regulator of tissue damage in cisplatin-induced AKI
  Xiong et al, 2021 [59]Cisplatin-induced AKI in Sprague-Dawley and Wistar ratsIntrarenal uncoupling protein (UCP) 1 inhibits intrarenal lipid clearance
Other types of AKI
  Xue et al, 2021 [61]Murine model of heat stroke-related AKIIntrarenal enrichment of unsaturated fatty acids