Metabolomics in Acute Kidney Injury: The Experimental Perspective

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.

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

“…Renal lipid toxicity resulting from abnormal lipid metabolism is an important pathological factor contributing to the occurrence and progression of AKI. 47 It is critically important to reduce intracellular lipid accumulation and promote degradation of lipid deposits in order to mitigate lipotoxic damage. Lipophagy is a cellular process by which lipid droplets are engulfed by autophagosomes, which subsequently fuse with lysosomes.…”

Deliverables from Metabolomics in Kidney Disease: Adenine, New Insights, and Implication for Clinical Decision-Making

“…Lack of awareness, as early CKD stages often remain asymptomatic, contributes to high morbidity and mortality. CKD also amplifies the mortality associated with other conditions like cardiovascular diseases, type 2 diabetes (T2DM), hypertension, and infections such as HIV, malaria, and COVID-19 [3,11,25,26]. AKI, common in hospitalized patients, involves sudden kidney function decline due to infections, medications, or dehydration.…”

“…Biochemical Pathways Associated with Kidney Diseases Metabolomics plays a pivotal role in unraveling the intricate biochemical pathways associated with kidney diseases. Metabolomics can provide a comprehensive analysis of small molecules or metabolites within biological samples, such as urine and blood, to gain insights into the metabolic changes that occur during the development and progression of kidney diseases [25][26][27][28][29][30]43] and serve as biomarkers that are associated with different etiologies of kidney diseases. By analyzing the pattern of metabolites, researchers can gain insights into the altered biochemical pathways in the kidneys with insights often not possible from reliance on transcriptomics and proteomics alone.…”

Metabolomics, the future of biomarkers?

“…For example, metabolomics allowed the identification of new prognostic biomarkers in traumatic brain injury patients that may serve as indicators for optimizing management [4]. Experimental data also showed promise in identifying the various phenomena leading to acute renal failure [5]. Multi-omics analysis also enabled us to identify biomolecules specific to non-survival in acute liver failure [6].…”