Table 1.

Summary of omics studies of SA-AKI.

Study	Omic technology	Methods/models	Major findings
Frank, 2013 (60)	Genomics-DNA microarray	1,264 patients with septic shock, of these, 887 white patients were randomly assigned to the discovery and validation cohort	5 SNPs were associated with SA-AKI: BCL2, SERPINA, SIK3 genes.
Vilander, 2017 (61)	Genomics-SNP genotyping	2567 patients without chronic kidney disease and with a genetic sample, 837 had sepsis and 627 had septic shock	SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.
Genga, 2018 (62)	Genomics-DNA polymorphisms	Two cohorts were retrospectively analyzed: Derivation Cohort (202 patients with sepsis enrolled at the Emergency Department from 2011 to 2014 in Vancouver, Canada); Validation Cohort (604 septic shock patients enrolled into the Vasopressin in Septic Shock Trial (VASST)).	CETP modulates HDL-C levels in sepsis. CETP genotype may identify patients at high-risk of sepsis-associated AKI.
Vilander, 2019 (63)	Genomics-Genotyping polymorphism	653 patients with sepsis, 300 had KDIGO stage 2 or 3 AKI and 353 did not (KDIGO Stage 0)	Association between short repeats of HMOX1 and AKI risk in sepsis patients.
Sun, 2020 (64)	Genomics-SNP genotyping	235 patients with AKI and 235 patients without AKI (No AKI)	SNPS in NFKB1 loci rs41275743 and RS4648143 are associated with the risk of AKI in sepsis patients.
Tran, 2011 (65)	Transcriptomics-gene expression microarray	Mice after intraperitoneal injection of LPS (Global knockouts and mice with the floxed PGC-1α allele have been previously described)	Restored expression of the mitochondrial biogenesis factor PGC-1α appears to be necessary for recovery from endotoxemic AKI.
Basu, 2011 (66)	Transcriptomics-gene expression microarray	179 children with septic shock and 53 age-matched normal controls	There were 21 unique gene probes upregulated in patients with SSAKI compared to patients without SSAKI.
Ge, 2017 (67)	Transcriptomics-gene expression microarray	Patients with sepsis induced AKI (n = 6), patients without sepsis AKI (n = 6), and healthy volunteers (n = 3)	miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups.
Hultström, 2018 (68)	Transcriptomics-gene expression microarray	Six high-quality microarray studies of renal gene expression after AKI	5,254 differentially expressed genes in at least one of the AKI models; MYC may be a central regulator of renal gene expression in tissue injury during AKI.
Tod, 2020 (69)	Transcriptomics-gene expression microarray	Mice after intraperitoneal injection of LPS	MiR-762 expression was significantly increased in the early stages of septic AKI, and clusters of miR-144/451 were upregulated at 24 h.
Holly, 2006 (70)	Urine proteomics-DIGE, MS	Rat CLP sepsis	A potential biomarker and drug target, Meprin-1-alpha, was identified in a septicaemic induced ARF rat model.
Maddens, 2012 (71)	Urine, plasma, tissue proteomics gel-free technique	Mice uterus ligation and E. coli inoculation	Urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice.
Wu, 2015 (72)	Tissue proteomics-DIGE, MALDI-TOF/TOF MS	Mouse CLP sepsis	Phosphorylated MYL12B can be used as a potential plasma biomarker for early diagnosis of SA-AKI.
Hinkelbein, 2017 (73)	Tissue proteomics-DIGE, MS	Rat CLP sepsis	MUP5 decreased in SA-AKI. Mitochondrial energy production and electron transport were found to be significantly correlated with proteins.
Hashida, 2017 (74)	Proteomics from hemofilter adsorbates- SDS PAGE, MS	20 patients with AKI on ICU admission and who received continuous renal replacement therapy (CRRT) as usual care between June 2012 and March 2014 were studied.	Three proteins, including carbonic anhydrase 1 (CA1) and leucine-rich α -2-glycoprotein (LRG1), were identified in all samples from patients with sepsis compared with those without sepsis.
Li, 2020 (75)	Urinary proteomics-MS	Rat CLP sepsis; Sepsis was validated in human patients	PARK7 and CDH16 have been identified as novel biomarkers for the early diagnosis of septic AKI.
Lin, 2020 (76)	Tissue global Proteomic and Phosphoproteomic-SDS PAGE, MS	Mouse CLP moderately severe sepsis	2,119 protein and 2950 phosphorus sites were identified; Several new and/or less studied S-AKI labeled proteins Hmgcs2 Serpin S100a8 and Chil3 were validated.
Waltz, 2016 (77)	Tissue (whole kidney) metabolomics-LC/MS	Mice CLP sepsis	CLP induced renal injury as evidenced by elevated serum creatinine, blood urea nitrogen, and cystatin C. Global energetic profile in sepsis showed an increase in glycolytic intermediates with decreased flux through the tricarboxylic acid (TCA) cycle. Multiple inflammatory markers were elevated in response to CLP. Levels of osmotic regulators varied, with an overall increase in pinitol, urea, and taurine in response to CLP.
Li, 2017 (78)	Tissue and serum metabolomics-1H NMR	Mice after intraperitoneal injection of LPS	Obvious decreases in betaine, taurine, lactate, glucose, and significant increases in 3-CP, acetoacetate, pyruvate, NADPH, creatine, creatinine, TMAO in LPS mice.
Rodrigues, 2018 (79)	Urine metabolomics-NMR	Rat CLP sepsis	1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals.
Garcia, 2019 (80)	Tissue, plasma, and urine metabolomics-NMR	Pigs infused with E. coli	Metabolic differences between control animals and septicemic animals: In renal tissue, lactic acid and niacin increased, while valine, aspartate, glucose and threonine decreased; Iso-glutamate n-acetyl glutamine n-acetyl aspartic acid and ascorbic acid increased, while inositol and phenylacetyl glycine decreased in urine; And In serum, lactate alanine pyruvate and glutamine increased, while valine glucose and betaine concentrations decreased.
Ping, 2019 (81)	Tissue metabolomics-GC-TOFMS	Rat after intraperitoneal injection of LPS	Metabolic disorders of taurine, pantothenic acid, and phenylalanine and phenylalanine in the renal cortex are associated with the development of SA-AKI.
Lin, 2020 (82)	Plasma metabolomics-GC/MS	Plasma samples from 31 patients with sepsis and 23 healthy individuals.	The downregulated energy, amino acid, and lipid metabolism found in our study may serve as a novel clinical marker for the dysregulated internal environment, particularly involving energy metabolism, which results in sepsis.