Metabolomics in Acute Kidney Injury: The Experimental Perspective

Daniel Patschan, Susann Patschan, Igor Matyukhin, Meike Hoffmeister, Martin Lauxmann, Oliver Ritter, Werner Dammermann

Abstract


Acute kidney injury (AKI) affects increasing numbers of in-hospital patients in Central Europe and the USA, the prognosis remains poor. Although substantial progress has been achieved in the identification of molecular/cellular processes that induce and perpetuate AKI, more integrated pathophysiological perspectives are missing. Metabolomics enables the identification of low-molecular-weight (< 1.5 kD) substances from biological specimens such as certain types of fluid or tissue. The aim of the article was to review the literature on metabolic profiling in experimental AKI and to answer the question if metabolomics allows the integration of distinct pathophysiological events such as tubulopathy and microvasculopathy in ischemic and toxic AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1940 until 2022. The following terms were utilized: “acute kidney injury” OR “acute renal failure” OR “AKI” AND “metabolomics” OR “metabolic profiling” OR “omics” AND “ischemic” OR “toxic” OR “drug-induced” OR “sepsis” OR “LPS” OR “cisplatin” OR “cardiorenal” OR “CRS” AND “mouse” OR “mice” OR “murine” OR “rats” OR “rat”. Additional search terms were “cardiac surgery”, “cardiopulmonary bypass”, “pig”, “dog”, and “swine”. In total, 13 studies were identified. Five studies were related to ischemic, seven studies to toxic (lipopolysaccharide (LPS), cisplatin), and one study to heat shock-associated AKI. Only one study, related to cisplatin-induced AKI, was performed as a targeted analysis. The majority of the studies identified multiple metabolic deteriorations upon ischemia/the administration of LPS or cisplatin (e.g., amino acid, glucose, lipid metabolism). Particularly, abnormalities in the lipid homeostasis were shown under almost all experimental conditions. LPS-induced AKI most likely depends on the alterations in the tryptophan metabolism. Metabolomics studies provide a deeper understanding of pathophysiological links between distinct processes that are responsible for functional impairment/structural damage in ischemic or toxic or other types of AKI.




J Clin Med Res. 2023;15(6):283-291
doi: https://doi.org/10.14740/jocmr4913

Keywords


AKI; Metabolomics; KRT; Recovery of kidney function; Survival

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