The Acute Disease Quality Initiative (ADQI) working group recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), but the prognosis and risk factors for early and late SA-AKI have not been studied.

This was a retrospective cohort study based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (v2.2). First, SA-AKI patients that met the new definition from the ADQI were screened, and then, the relationships between SA-AKI occurrence time and relevant clinical parameters were analyzed.

After propensity score matching, 1,090 early SA-AKI (AKI occurring within 48 h of sepsis diagnosis) cases and late SA-AKI (AKI occurring between 48 h and 7 days after sepsis diagnosis) cases were identified. Compared with late SA-AKI patients, early SA-AKI patients had no significant differences in all-cause mortality at 28 days, 60 days or 180 days, renal replacement therapy (RRT) rates; or major adverse kidney events at 30 days (MAKE-30). However, the renal recovery of early SA-AKI patients was significantly better than that of late SA-AKI patients, their lengths of hospital stay and intensive care unit stay were significantly shorter, and the number of patients with positive fluid balance was lower, but the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotoxic antibiotics and the incidence of septic shock were higher. In addition, there was a difference in the number of patients with early and late SA-AKI at highest AKI stages 1 and 3. Data analysis also revealed that liver disease, cancer, highest AKI stage 3 and septic shock were associated with renal nonrecovery.

Although there was no significant difference in mortality between early and late SA-AKI patients, there were significant differences in renal recovery, positive fluid balance, nephrotoxic antibiotic use, septic shock and AKI stage. Therefore, the classification of early and late SA-AKI has certain scientific and rational validity, but whether the two have different clinical outcomes and pathogeneses requires further study.

Ischemia-reperfusion injury (IRI) is closely associated with numerous severe postoperative complications, including acute rejection, delayed graft function (DGF) and graft failure. Macrophages are central to modulating the aseptic inflammatory response during the IRI process. The objective of this study is to conduct an analysis of the developmental and differentiation characteristics of macrophages in IRI, identify distinct molecules subtypes of IRI, and establish robust predictive strategies for DGF and graft survival.

We analyzed scRNA-Seq data from GEO database to identify macrophage sub-clusters specific to renal IRI, and use the hdWGCNA algorithm to screen gene modules closely associated with this sub-cluster. Integrating these module genes with the results from bulk RNA-Seq differential analysis to obtain hub genes, and delineating the different IRI molecular subtypes through consensus clustering based on the expression profiles of hub genes. Innovatively, the gene expression matrix was transformed into a unique graphic pixel module and applied advanced computer vision processing algorithms to construct a DGF predictive model. Additionally, we also employed 111 combinations of 10 machine learning algorithms to develop a predictive signature for graft survival. Finally, we validated the expression of the key gene ANXA1 in a mouse IRI model using qRT-PCR, WB, and IHC.

This study successfully identified a subset of macrophages closely associated with renal IRI, and cell communication and pseudo-time analysis implied that they may be instrumental in both the maintenance and exacerbation of the IRI process. Utilizing the expression patterns of hub genes, recipients can be clustered into two subtypes (CI and C2) with unique clinical and molecular features. We innovatively applied deep learning algorithms to construct a model for DGF prediction, which can effectively mitigate batch effects among IRI recipients. Compared to other existing models, our model demonstrated superior performance with AUC of 0.816 and 0.845 in the training and validation set. Furthermore, we also used the random survival forest algorithm to develop a high-precision predictive signature for graft failure. The mouse IRI model confirmed a marked upregulation of ANXA1 mRNA and protein expression in renal tissue following IRI.

This study successfully revealed the macrophage sub-cluster closely associated with renal IRI. Two distinct IRI subgroups with different characteristics were identified and robust strategies were constructed for predicting DGF and graft survival, which can offer potential therapeutic targets for the treatment of IRI and reference for early prevention of various postoperative complications.

Patients who develop sepsis-associated acute kidney injury (SAKI) in the intensive care unit face a significantly elevated mortality risk. The lactate-to-albumin ratio (LAR) has been utilized as an important marker for the occurrence and development of various diseases. Nevertheless, the association between LAR and SAKI remains inadequately explored. This study seeks to investigate the connection between the LAR and SAKI.

Patients identified with SAKI were selected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. LAR was recorded at the time of admission, with the primary endpoint being the development of AKI within 7 days following the sepsis diagnosis. Logistic regression and subgroup analyses were utilized to assess the relationship between LAR and SAKI.

The final analysis incorporated data from 4,113 patients retrieved from the MIMIC-IV database. Logistic regression analysis revealed that a 1-unit increase in LAR was linked to a 49% rise in the incidence of SAKI (95% confidence interval, 1.27 to 1.76; P < 0.001). These findings were further validated through subgroup analyses, confirming their robustness.

Higher LAR at admission was independently associated with an increased risk of SAKI.

Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, is reported to facilitate inflammation and fibrosis in various tissues including the kidneys. Ischemia/reperfusion (I/R) is a major process of acute kidney injury. To investigate whether SPARC inhibition might attenuate renal I/R injury, we injected small interfering RNA (siRNA) targeting SPARC into male BALB/c mice one day before 45 min of renal ischemia followed by 72 h of reperfusion. Serum creatinine concentration, blood urea nitrogen, histological tubular damage, tubulointerstitial fibrosis, and expression of collagen I and transforming growth factor-β were increased after I/R. Expression of 4-hydroxy-2-nonenal, an oxidative stress marker, and the inflammatory cytokines monocyte chemoattractant protein-1 and tumor necrosis factor-α, were also upregulated in I/R kidneys. Overexpression of SPARC mRNA was observed after I/R, and immunohistochemistry revealed that SPARC was localized mainly in damaged tubuloepithelial cells. Additionally, a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) expression colocalized with SPARC. Injection of siRNA targeting SPARC attenuated renal dysfunction, histological abnormalities, collagen deposition, oxidative stress, and renal inflammation. In addition, SPARC gene knockdown suppressed the I/R-induced increases in ADAMTS1 and matrix metalloproteinase-2/9 expression. In conclusion, I/R-induced SPARC could be a novel therapeutic target against acute kidney injury.

To investigate the molecular mechanism by which the miRNA let-7a regulates renal tubular epithelial cell apoptosis by influencing the activity of the PI3K/Akt pathway, which is involved in the development of sepsis-associated acute kidney injury (SA-AKI).

A sepsis-associated acute kidney injury model was constructed in vitro and in vivo using LPS, and the expression of the miRNA let-7a and activation of the PI3K/Akt pathway were detected in SA-AKI. Apoptosis marker molecules and inflammatory factor expression were detected by transfecting miRNA let-7a mimics with LPS-stimulated human renal tubular epithelial cells (HKCs) or using the PI3K/Akt pathway inhibitor LY294002. Bioassay analysis elucidated the relationship between miRNA let-7a and the PI3K/Akt signaling pathway. The mechanism was validated in primary renal tubular epithelial cells.

In the in vivo and in vitro models, miRNA let-7a expression was significantly reduced, and the PI3K/Akt pathway was activated. When miRNA let-7a was overexpressed or the PI3K/Akt pathway was inhibited, the inflammatory response of renal tubular epithelial cells was attenuated. Bioassay analysis verified that the miRNA let-7a binds to the PI3K/Akt signaling pathway. The miRNA let-7a-PI3K/Akt regulatory axis regulates the apoptosis of renal tubular epithelial cells in primary tubular epithelial cells.

The miRNA let-7a regulates inflammation and apoptosis in renal tubular epithelial cells by affecting the activity of the PI3K/Akt pathway in the development of sepsis-associated acute kidney injury.

In critically ill elderly patients, malnutrition is a common comorbidity. The Geriatric Nutritional Risk Index (GNRI) is a straightforward tool for evaluating the nutritional status of elderly individuals. The association between GNRI score and unfavorable health outcomes has been established. However, no studies have yet elucidated the relationship between GNRI score and sepsis-related acute kidney injury (S-AKI).

We sourced patient data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were divided into four groups based on their GNRI score using quartile analysis. The main objective of this study was to investigate the 28-day mortality rate. Secondary study outcomes were the incidence of severe AKI, length of stay in the intensive care unit, and days in the hospital. To evaluate the association between GNRI score and study outcomes, we used a Cox proportional hazards regression model and restricted cubic splines. Kaplan-Meier curves were used to compare the outcomes in each group.

A total of 4515 elderly patients with S-AKI were included in this study. Patients were categorized into four groups according to GNRI quartile: Q1 (< 78.92), Q2 (78.92-84.88), Q3 (84.88-90.84), and Q4 (> 90.84). Overall 28-day mortality was 29.5%. Patients with a low GNRI were predominantly women, and had a low body mass index. After controlling for confounding factors, GNRI score emerged as an independent predictor of 28-day mortality among elderly patients with S-AKI (Q4 vs. Q1: hazard ratio 0.74, 95% confidence interval 0.63-0.87; p < 0.001). Restricted cubic spline analysis revealed a linear relationship between GNRI and 28-day mortality (p for non-linearity = 0.207), and this association remained consistent across all subgroup analyses.

The GNRI is an important nutritional assessment tool, and is useful in predicting the prognosis of critically ill elderly patients with S- AKI.

A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 has previously been demonstrated. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in critically ill patients with AKI compared to similar patients without AKI.

A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 mL/kg Ringer's Acetate (Baxter). Arithmetic means of mean arterial pressures (MAP) recorded before and after plasma infusion were compared. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects.

Nine patients with AKI and eight without were included in the study. The hemodynamic response to plasma expansion was similar in both groups, with increases in MAP by 9 mmHg (95% CI 0.5-18) and 15 mmHg (95% CI 5-24) in patients with and without AKI, respectively. Total renal perfusion and cortical perfusion were not significantly changed by plasma expansion in either group. There was a reduction of medullary perfusion in patients without AKI from 55 (95% CI 39-79) to 34 (95% CI 24-48) mL/min/100 g (p = .0027).

Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19, with or without AKI.

Most cases of acute kidney injury (AKI) resolve within 72 h. However, a small number of patients with persistent severe AKI have significantly worse outcomes. We sought to describe the occurrence, impact on outcome and risk factors associated with persistent severe AKI in critically ill patients using a standardized definition.

Retrospective cohort study, investigating critically ill patients admitted to one of 16 hospitals from October 2010 to June 2018. We defined persistent severe AKI as Kidney Disease: Improving Global Outcomes stage 2-3 AKI that progressed to and persisted at stage 3 for ≥ 72 h. Risk factors for persistent severe AKI and its association with outcomes were assessed using the super learner algorithm, integrating LASSO logistic regression and XGBoost, and multivariate logistic regression or Cox proportional hazards models, using no persistent severe AKI as the comparator.

Of 65,119/190,550 (34.2%) patients with stage 2-3 AKI, 8,059 (12.4%) had persistent severe AKI. Severe, early community-acquired AKI, high fluid balance, multiple organ dysfunction, sepsis and shock were important risk factors. Persistent severe AKI was associated with an increased risk of 90-day mortality (HR 1.5, 95% CI 1.4-1.6), hospital readmission (OR 2.0, 95% CI 1.8-2.3), and with a lower probability of renal recovery (OR 0.14, 95% CI 0.13, 0.15).

Persistent severe AKI is an uncommon, but important complication in critically ill patients, associated with an increased risk of renal non-recovery, hospital readmission and death, and an important target for therapeutic development.

Sepsis-associated acute kidney injury (S-AKI) has a significant impact on patient survival, with continuous renal replacement therapy (CRRT) being a crucial intervention. However, the optimal timing for CRRT initiation remains controversial.

Using the MIMIC-IV database for model development and the eICU database for external validation, we analyzed patients with S-AKI to compare survival rates between early and late CRRT initiation groups. Propensity score matching was performed to address potential selection bias. Subgroup analyses stratified patients by disease severity using SOFA scores (low ≤10, medium 11-15, high >15) and creatinine levels (low ≤3 mg/dL, medium 3-5 mg/dL, high >5 mg/dL). Multiple machine learning models were developed and evaluated to predict patient prognosis, with Shapley Additive exPlanations (SHAP) analysis identifying key prognostic factors.

After propensity score matching, late CRRT initiation was associated with improved survival probability, but led to increased hospital and ICU stays. Subgroup analyses showed consistent trends favoring late CRRT across all SOFA categories, with the most pronounced effect in high SOFA scores (>15, p = 0.058). The GBM model demonstrated robust predictive performance (average C-index 0.694 in validation and test sets). SHAP analysis identified maximum lactate levels, age, and minimum SpO2 as the strongest predictors of mortality, while CRRT timing showed relatively lower impact on outcome prediction.

While later initiation of CRRT in S-AKI patients was associated with improved survival, this benefit comes with increased healthcare resource utilization. The clinical parameters, rather than CRRT timing, are the primary determinants of patient outcomes, suggesting the need for a more personalized approach to CRRT initiation based on overall illness severity.

Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.

Sepsis-induced acute kidney injury (AKI) is considered as a life-threatening complication of sepsis. The purpose of this study is to clarify the involvement of annexin A3 (ANXA3) in sepsis-related AKI.

Lipopolysaccharide (LPS) was used to establish a cell model based on HK2 cells. ANXA3 expression was quantified through quantitative real-time polymerase chain reaction. Cell proliferative capacities were assessed through 5-ethynyl-2'-deoxyuridine proliferation, cell counting kit-8, and colony formation experiments. Flow cytometry was utilized to analyze apoptotic cells. Inflammatory and oxidative stress indicators were measured by employing corresponding commercial assay kits. Endoplasmic reticulum (ER) stress markers were quantified through western blot analysis.

ANXA3 levels were significantly elevated in HK2 cells treated with LPS and in serum samples obtained from patients with AKI and sepsis (P < 0.001). LPS treatment exacerbated cellular damage, leading to increased ER and oxidative stresses, apoptosis, and inflammation, whereas knocking down ANXA3 significantly reversed these changes (P < 0.001).

Interference with ANXA3 protected HK2 cells from LPS-induced cell injury through inhibiting inflammation, oxidative stress, apoptosis, and ER stress.

Sepsis is a major cause of mortality among critical patients. Acute kidney injury (AKI) is the common complication in patients with sepsis, characterized by rapid deterioration of renal function. The purpose of this study is to assess the impact of inhaling high concentration hydrogen on septic mice with AKI and to examine the involvement of mitochondria in this process. High concentration hydrogen does not cause hypoxia and can alleviate AKI and improve 7-day survival in septic mice. Inflammatory factors are markedly elevated in the serum and renal tissues in CLP group which are dramatically down-regulated by hydrogen. The activities of both antioxidant enzymes are significantly reduced after CLP, whereas hydrogen markedly increases the activities of SOD and CAT. MMP is found to be significantly lower in CLP group whereas this effect is reversed by hydrogen. The trend of ATP content in renal tissues corresponded with that of MMP. There is a substantial downregulation of PGC-1α, Nrf2, and TFAM protein in CLP group. Drp1 expression is significantly higher in CLP group compared to Sham group, while the opposite trend is observed for MFN2. Hydrogen can reverse these changes. Inhalation of high concentration hydrogen can improve acute kidney injury, 7-day survival, inflammatory response and oxidative stress in septic mice. The mechanism may be related to inhibit renal mitochondrial fission and promote mitochondrial fusion and biogenesis.

This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI.

The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot.

Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group.

TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Background Sepsis-induced acute kidney injury (S-AKI) is a common complication in critically ill patients. Therefore, reliable biomarkers for predicting S-AKI outcomes are necessary. Serum cell-free DNA (cfDNA) is a circulating extracellular DNA fragment used as a noninvasive screening tool for many diseases, including sepsis. This study aimed to investigate the prognostic value of cfDNA in S-AKI patients and its relationship with some other parameters.Methods A total of 89 S-AKI patients admitted to the intensive care unit (ICU) from June 2021 to December 2021 were enrolled in this study. The patients were categorized into the low cfDNA group (< 855 ng/ml) and high cfDNA group (≥ 855 ng/ml) and were followed up for three months. CfDNA was extracted from serum and quantified using Quant-iT PicoGreen dsDNA Reagent.Results Overall survival was significantly lower in the high cfDNA group than in the low cfDNA group (Log-Rank p = 0.012). Univariate Cox proportional hazard model showed that cfDNA was significantly associated with all-cause mortality (HR [hazard ratio] 2.505, 95% CI [95% confidence interval] 1.184-5.298, p = 0.016). Also, serum cfDNA was a significant risk factor for all-cause mortality after adjusting for covariates (HR 2.191, 95% CI 1.017-4.721, p = 0.045). Moreover, cfDNA was positively correlated with several baseline parameters, including serum creatine, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and International Normalized Ratio.Conclusion High serum cfDNA level is associated with higher mortality among the S-AKI population, indicating that cfDNA is a valuable biomarker for S-AKI prognosis.

The molecular mechanism underlying the protective effects of DEX against sepsis-induced acute kidney injury (SAKI) remains to be elucidated.

We established S-AKI models in vivo via CLP and in vitro with LPS-induced HK-2 cells.

The Nrf2/SLC7A11/FSP1/CoQ10 pathway was inhibited in S-AKI both in vitro and in vivo. The overexpression of Nrf2 inhibited LPS-induced ferroptosis by activating the SLC7A11/FSP1/CoQ10 pathway. DEX ameliorated kidney tissue damage, as determined by a decrease in BUN, Cr, and inflammatory factor levels, along with renal tubule vacuolation and inflammatory cell infiltration in S-AKI mice. Additionally, DEX treatment significantly ameliorated ferroptosis in S-AKI in vitro and in vivo, as indicated by an improvement in mitochondrial shrinkage and disruption of cristae, a decrease in iron, ROS, MDA, and 4-HNE levels, and an increase in GSH and GPX4 levels. Mechanistically, DEX treatment restored the reduction of Nrf2 expression and nuclear translocation in S-AKI, as well as, the levels of downstream SLC7A11, FSP1, and CoQ10. Knocking down Nrf2 in vitro and administering brusatol in vivo eliminated the protective effect of DEX against S-AKI.

DEX mitigated ferroptosis and attenuated S-AKI by activating the Nrf2/SLC7A11/FSP1/CoQ10 pathway. Abbreviation: CLP: Cecal ligation puncture; LPS: Lipopolysaccharide; Nrf2: Nuclear factor-erythroid- 2-related factor 2; SLC7A11: Solute carrier family 7 member 11; FSP1: Ferroptosis suppressor protein 1; CoQ10: Coenzyme Q10; BUN: Blood urea nitrogen; Cr: Serum creatinine; ROS: Reactive oxygen species; MDA: Malondialdehyde; 4-HNE: 4-hydroxynonenal; GSH: Hlutathione; GPX4: Glutathione peroxidase 4.

Abnormal Wnt5a expression is associated with dysregulated inflammation and organ dysfunction. However, the effect of Wnt5a activation on the duration of organ dysfunction remains unclear. This prospective study investigated the association between Wnt5a levels and persistent acute kidney injury (AKI) in patients with urosepsis. Serum creatinine and Wnt5a levels were measured on days 1 and 5 and at discharge in 87 patients diagnosed with urosepsis. Patients with urosepsis were classified into an improving acute kidney injury (AKI) group and a persistent or worsening AKI group according to the AKI stage on days 1 and 5. AKI recovery was defined as a discharge-to-baseline serum creatinine ratio of <1.5. Twenty-eight patients with urosepsis (32.2%) had persistent or worsening AKI, and their Wnt5a levels were higher on days 1 and 5 and at discharge than those with improving AKI. The association between Wnt5a levels and persistent or worsening AKI was maintained after adjusting for age, sex, baseline serum creatinine levels, and disease severity. Moreover, elevated Wnt5a levels were associated with an increased risk of major adverse kidney events. High Wnt5a levels at discharge were associated with unrecovered AKI and participants with AKI recovery had a steeper Wnt5a slope over time than those without recovery, irrespective of age, sex, baseline serum creatinine level, or disease severity. Assessment of Wnt5a expression was helpful in predicting AKI persistence and adverse outcomes in patients with urosepsis. Therefore, Wnt5a may serve as a valuable bio-marker for identifying the risk of persistence of AKI.

Despite the clinical importance of sepsis-associated acute kidney injury (SA-AKI), little is known about its epidemiology. We aimed to investigate the incidence and outcomes of SA-AKI, as well as the risk factors for mortality among patients with severe SA-AKI in critically ill patients.

This secondary multicenter, observational, prospective cohort analysis of sepsis in South Korea evaluated patients aged ≥ 19 years admitted to intensive care units with a diagnosis of sepsis. The primary outcome was the incidence of SA-AKI, defined using the new consensus definition of the Acute Disease Quality Initiative 28 Workgroup. Secondary outcomes were in-hospital mortality and risk factors for in-hospital mortality.

Between September 2019 and December 2022, 5100 patients were admitted to intensive care units with a diagnosis of sepsis, and 3177 (62.3%) developed SA-AKI. A total of 613 (19.3%), 721 (22.7%), and 1843 (58.0%) patients had stage 1, 2, and 3 SA-AKI, respectively. Severe SA-AKI (stages 2 and 3 combined) was associated with an increased risk of in-hospital mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle was associated with a decreased risk of in-hospital mortality in severe SA-AKI (adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.79; P < 0.001).

Of the patients admitted to the intensive care unit for sepsis, 62.3% developed SA-AKI. Severe SA-AKI was associated with an increased risk of mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle can potentially improve outcomes in these patients.

The predictive value of the Systemic Immune-Inflammation Index (SII) on mortality in patients with sepsis-associated acute kidney injury (S-AKI) remains unclear. This study aims to investigate the predictive value of SII levels at the Intensive Care Unit (ICU) on the 28-day mortality of S-AKI patients.

S-AKI patients admitted to the ICU of Henan Provincial People's Hospital from January 1, 2023, to December 31, 2023. Patients who were diagnosed with S-AKI were divided into survival and death groups based on their 28-day outcome after ICU admission. Using receiver operating characteristic (ROC) curves to determine the best cut-off values and prognostic abilities of various parameters. Kaplan-Meier survival curves describe the 28-day survival of patients after ICU admission. Cox regression analysis identified the main risk factors associated with mortality in S-AKI patients, constructing a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability of this model.

A total of 216 patients with S-AKI were included. ROC analysis showed that SII had the highest predictive value for mortality risk in S-AKI patients after ICU admission. Compared with the low-SII group, the high-SII group had higher 28-day (86.7% vs 32.4%, respectively, P <0.001) mortality rate. Based on Cox regression analysis, a nomogram predictive model was constructed, including age, respiratory failure, SII levels, number of organ dysfunctions at ICU admission, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHEII). The C-index for predicting the 28-day survival rate was 0.682. Decision curve analysis indicated a high level of clinical predictive efficacy.

SII serves as a potential biomarker for predicting the prognosis of S-AKI patients. The constructed nomogram prognostic model can aid in assessing the prognosis of S-AKI patients.

Mitochondrial dysfunction contributes to septic acute kidney injury (S-AKI), making mitochondrial protection a potential therapeutic strategy. This study investigates the effects of S14G-humanin (HNG) in S-AKI, utilizing 4D-label-free and parallel reaction monitoring (PRM) techniques for proteomic analysis. An S-AKI model was created in male C57BL/6 mice using lipopolysaccharide (LPS) injection, followed by HNG administration. After 24 h, kidney tissues were analyzed for histology, biochemistry, mitochondrial function, and proteomics. HNG treatment improved renal function, reduced tubular injury, and decreased pro-inflammatory cytokines and oxidative stress markers. Proteomic analysis identified 5900 proteins, with 5111 quantifiable. HNG altered the expression of 132 proteins, with 18 selected for PRM validation. Ten of these proteins were linked to key pathways, including fatty acid degradation and PPAR signaling. This study is the first to show HNG's protective effects in S-AKI, providing insights into its mechanisms through advanced proteomic techniques.

This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study seeks to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients with SA-AKI.

This retrospective cohort study utilized clinical data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including all patients with SA-AKI admitted to the intensive care unit for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan-Meier curves and Cox regression models were employed to evaluate the association between serum ferritin levels and mortality. Subgroup and sensitivity analyses were performed to verify the robustness of the results.

In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results indicated that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, patients in the highest quartile of serum ferritin had significantly higher 28-day mortality compared to those in the reference group (the first quartile of ferritin levels). After adjusting for various factors, the fully adjusted hazard ratio was 1.92 (95% CI: 1.24-2.96, p = 0.003).

In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.

Septic shock is defined as sepsis with hypotension requiring vasopressors to maintain a mean arterial pressure above 65 mmHg and having a serum lactate level of more than 2 mmol/L despite adequate volume resuscitation as per the Sepsis-3 criteria. Continuous renal replacement therapy (CRRT) is commonly utilized in septic shock patients for the treatment of acute kidney injury as well as for modulating immune response and maintaining hemodynamic stability.

We looked at the National Inpatient Sample database in 2019. We identified adult patients with septic shock as the primary diagnosis using the International Classification of Diseases, 10th revision, clinical modification codes R65.21 and R78.81, and subbranches of Aa41, A40, and R60. STATA 18 (StataCorp, College Station, TX) was used to perform logistic multivariate regression analyses.

A total of 15,794 adults who were admitted for septic shock as the primary diagnosis underwent CRRT. The mean age of the patients was 61.7 years. The overall mortality rate was 57% (N = 9,002). An increase in age by one year was associated with a 1% increase in mortality (p = 0.001). The presence of hypertension increased mortality by 29% (N = 6,391) (p = 0.028). Interestingly, preexisting diabetes mellitus improved mortality by 37% (N = 3331) (p = 0.001).The outcome of CRRT was better in patients with chronic kidney disease, with a 26% improvement in mortality (N = 2341) (p = 0.001). A significant improvement in outcome (29% decrease in mortality, p=0.013) and 31% reduction in hospital length of stay (p = 0.008) was noted with CRRT initiated on day 2 of hospitalization.

This study highlights that the approximate time of initiation of CRRT for optimal benefit of the treatment is between 24 and 48 hours of hospitalization. This study emphasizes the prognostic factors of a standard therapy, which can serve as a basis for clinical decision-making.

Diagnostic and prognostic values of Kruppel-like factor 5 (KLF5) and Runt-related transcription factor 1 (RUNX1) were determined in sepsis-induced acute kidney injury (SI-AKI). The study included 120 septic patients and set two groups: SI-AKI group (n = 60) or non-AKI group (n = 60). Fasting venous blood was drawn, and KLF5 and RUNX1 levels were measured. The receiver operating characteristic curve was plotted for diagnostic evaluation of KLF5 and RUNX1 in SI-AKI. The correlation between KLF5 and RUNX1 and serum creatinine (Scr), cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1) were assessed by Pearson method. Predictive values of KLF5 and RUNX1 in 28-day survival of SI-AKI patients were considered by Kaplan-Meier survival curves and multivariate Cox regression analysis. Serum KLF5 and RUNX1 in SI-AKI patients were upregulated. Serum KLF5 and RUNX1 were of high diagnostic value in distinguishing SI-AKI patients from non-AKI patients. KLF5 and RUNX1 were in a positive correlation with Scr, Cys-C, and KIM-1, respectively. The 28-day survival of SI-AKI patients with high serum KLF5 or RUNX1 expression was poor, and serum KLF5 and RUNX1 expression were independently correlated with SI-AKI patients' survival. KLF5 and RUNX1 have diagnostic and prognostic values in SI-AKI patients.

Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (α, β, γ, δ) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record.

Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype?

This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI and AKD and phenotype.

Among 1,090 eligible patients, 543 patients (50%) had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the δ and β phenotypes (78% and 71%, respectively) and the lowest in the α phenotype (26%; P < .001). AKD occurred most often in the δ phenotype (41%) and least often in the α phenotype (8%; P < .001). The highest frequencies of CKD and of AKI on CKD were found in the β phenotype (53% and 38% respectively; P < .001 for both). In the multivariable logistic regression models (α phenotype as reference), δ phenotype showed the strongest association with AKI (OR, 12.33; 95% CI, 7.81-19.47; P < .001) and AKD (OR, 9.18; 95% CI, 5.44-15.51; P < .001).

The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotypes β and δ. Phenotype β showed a higher level of underlying CKD that predisposed patients to new AKI. The α and γ phenotypes showed lower frequencies of AKI and less progression to AKD.

Acute kidney injury (AKI) is a prevalent and potentially life-threatening complication characterized by a high incidence and mortality. A large number of studies have emphasized the role of ferroptosis in AKI. Moreover, FBXW7, a ubiquitin ligase, has been implicated in acute organ injury. Analysis of the GEO database (GSE98622) revealed increased FBXW7 mRNA levels in the kidney following ischemia‒reperfusion (IR). However, the role of FBXW7 in AKI has not been elucidated. Therefore, this study aimed to investigate the role of FBXW7 in IR-AKI and its underlying mechanisms. Here, we found that IR could induce AKI and increase FBXW7 expression, while the ferroptosis inhibitor Fer-1 alleviated AKI and decreased FBXW7 expression. Furthermore, we treated HK-2 cells with hypoxia for 12 h and reoxygenation for 4 h (H12R4) to simulate IR-AKI and investigated the impact of modulating FBXW7 expression on ferroptosis by employing ferroptosis-related agonists or inhibitors. Our findings revealed that H12R4 induced HK2 ferroptosis and increased the expression of FBXW7. FBXW7 overexpression in control cells exacerbated erastin-induced ferroptosis, and FBXW7 knockdown inhibited ferroptosis in H12R4-treated cells. Mechanistically, we confirmed that FBXW7 can bind to GPX4, a key molecule that inhibits ferroptosis. The half-life of the GPX4 protein decreased after FBXW7 overexpression, GPX4 ubiquitination increased after H12R4, and GPX4 degradation decreased after FBXW7 knockdown. In conclusion, our results indicated that FBXW7 plays an important role in the development of IR-AKI by promoting ferroptosis through the downregulation of GPX4 expression. This study provides new insight into FBXW7 as a potential target for treating AKI.

Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients.

We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital.

198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value.

The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.

Sepsis-associated acute kidney injury (SA-AKI) increases the risk of death in patients with sepsis, and its major pathological change is the death of renal tubular cells. However, the mechanism of its occurrence remains unclear. Sepsis can lead to circadian dysregulation, and the rhythm gene NFIL3 has been reported to regulate lipid metabolism. There is compelling evidence that has demonstrated that lipid peroxidation can cause cellular ferroptosis. In this study, we established the in vitro and in vivo models of SA-AKI and confirmed the presence of ferroptosis of the renal tubular epithelial cells in SA-AKI. In addition, analysis of the GEO database showed that NFIL3 was highly expressed in sepsis patients and was highly correlated with the key molecule of ferroptosis, ACSL4. The in vitro and in vivo data suggested that NFIL3 was involved in ferroptosis and inflammation in SA-AKI. Subsequently, loss-of-function experiments revealed that NFIL3 knockdown attenuated ferroptosis and inflammation in renal tubular epithelial cells by downregulating ACSL4 expression, thus protecting SA-AKI. In conclusion, this study is the first to illustrate the involvement of the rhythm gene NFIL3 in SA-AKI, providing new insights and potential therapeutic targets for SA-AKI.

Normal saline is commonly used for resuscitation in sepsis patients but has a high chloride content, potentially increasing the risk of acute kidney injury (AKI). This study evaluated risk factors and developed a predictive risk score for AKI in sepsis patients treated with normal saline.

This retrospective cohort study utilized the medical and electronic health records of sepsis patients who received normal saline between January 2018 and May 2020. Predictors of AKI used to construct the predictive risk score were identified through multivariate logistic regression models, with discrimination and calibration assessed using the area under the receiver operating characteristic curve (AUROC) and the expected-to-observed (E/O) ratio. Internal validation was conducted using bootstrapping techniques.

AKI was reported in 211 of 735 patients (28.7%). Eight potential risk factors, including norepinephrine, the Acute Physiology and Chronic Health Evaluation II score, serum chloride, respiratory failure with invasive mechanical ventilation, nephrotoxic antimicrobial drug use, history of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use, history of liver disease, and serum creatinine were used to create the NACl RENAL-Cr score. The model demonstrated good discrimination and calibration (AUROC, 0.79; E/O, 1). The optimal cutoff was 2.5 points, with corresponding sensitivity, specificity, positive predictive value, and negative predictive value scores of 71.6%, 72.5%, 51.2%, and 86.4%, respectively.

The NACl RENAL-Cr score, consisting of eight critical variables, was used to predict AKI in sepsis patients who received normal saline. This tool can assist healthcare professionals when deciding on sepsis treatment and AKI monitoring.

Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with poor prognosis. We aimed to build a machine learning (ML)-based clinical model to predict 1-year mortality in patients with SA-AKI.

Six ML algorithms were included to perform model fitting. Feature selection was based on the feature importance evaluated by the SHapley Additive exPlanations (SHAP) values. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminatory ability of the prediction model. Calibration curve and Brier score were employed to assess the calibrated ability. Our ML-based prediction models were validated both internally and externally.

A total of 12,750 patients with SA-AKI and 55 features were included to build the prediction models. We identified the top 10 predictors including age, ICU stay and GCS score based on the feature importance. Among the six ML algorithms, the CatBoost showed the best prediction performance with an AUROC of 0.813 and Brier score of 0.119. In the external validation set, the predictive value remained favorable (AUROC = 0.784).

In this study, we developed and validated a ML-based prediction model based on 10 commonly used clinical features which could accurately and early identify the individuals at high-risk of long-term mortality in patients with SA-AKI.

Acute kidney injury (AKI) is common in hospitalized patients and results in significant morbidity and mortality. The objective of the study was to explore the systemic immune response of intensive care unit patients presenting with AKI, especially the association between immune profiles and persistent AKI during the first week after admission following various types of injuries (sepsis, trauma, surgery, and burns).

REALAKI is an ancillary analysis of the REAnimation Low Immune Status Marker (REALISM) cohort study, in which 359 critically ill patients were enrolled in three different intensive care units. Patients with end-stage renal disease were excluded from the REALAKI study. Clinical samples and data were collected three times after admission: at day 1 or 2 (D1-2), day 3 or 4 (D3-4) and day 5, 6 or 7 (D5-7). Immune profiles were compared between patients presenting with or without AKI. Patients with AKI at both D1-2 and D5-7 were defined as persistent AKI. A multivariable logistic regression model was performed to determine the independent association between AKI and patients' immunological parameters.

Three hundred and fifty-nine patients were included in this analysis. Among them, 137 (38%) were trauma patients, 103 (29%) post-surgery patients, 95 (26%) sepsis patients, and 24 (7%) were burn patients. One hundred and thirty-nine (39%) patients presented with AKI at D1-2 and 61 (20%) at D5-7. Overall, 94% presented with persistent AKI at D5-7. Patients with AKI presented with increased pro and anti-inflammatory cytokines and altered innate and adaptive immune responses. The modifications observed in the immune profiles tended to be more pronounced with increasing KDIGO stages. In the logistic regression model, a statistically significant association was observed at D1-2 between AKI and CD10lowCD16low immature neutrophils (OR 3.03 [1.7-5.5]-p < 0.001). At D5-7, increased interleukin-10 (IL-10) levels and reduced ex vivo TNF-α production after LPS stimulation were significantly associated with the presence of AKI (OR 1.38 [1.12-1.71]-p = 0.001 and 0.51 [0.27-0.91]-p = 0.03, respectively). Patients who recovered from AKI between D1-2 and D5-7 compared to patients with persistent AKI at D5-7, tended to correct these alterations.

Following various types of severe injuries, early AKI is associated with the initial inflammatory response. Presence of AKI at the end of the first week after injury is associated with injury-induced immunosuppression.

Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial.

We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction.

Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03).

Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.

Histone lactylation is a metabolic stress-related histone modification. However, the role of histone lactylation in the development of sepsis-associated acute kidney injury (SA-AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA-AKI, which is reported in this study. Furthermore, this lactate-dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho-associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor-κB (NF-κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA-AKI and reportes a novel post-translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA-AKI.

Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan dysfunction. Sepsis-associated acute kidney injury (AKI) is a significant contributor to patient morbidity and mortality. The connection between AKI and thromboinflammation is largely due to unique aspects of the renal vasculature. Specifically, the interaction between blood cells with the endothelial, glomerular, and peritubular capillary systems during thromboinflammation reduces oxygen supply to tubular epithelial cells. Previous studies have focused on tubular epithelial cell damage due to hypoxia, oxidative stress, and nephrotoxins. Although these factors are pivotal in acute tubular injury or necrosis, recent studies have demonstrated that AKI in sepsis encompasses a mixture of tubular and glomerular damage subtypes. In cases of sepsis-induced coagulopathy, thromboinflammation within the glomerulus and peritubular capillaries is an important pathogenic mechanism for AKI. Unfortunately, and despite the use of renal replacement therapy, the development of AKI in sepsis continues to be associated with high morbidity, mortality, and clinical challenges requiring alternative approaches. This review introduces the important role of thromboinflammation in AKI pathogenesis and details innovative vascular-targeting therapeutic strategies.

Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI.

Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate.

This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis.

NCT05900284.

Sepsis-induced acute kidney injury (AKI) is a common complication in patients with severe illness and leads to increased risks of mortality and chronic kidney disease. We investigated the association between monocyte distribution width (MDW), red-blood-cell volume distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), sepsis-related organ-failure assessment (SOFA) score, mean arterial pressure (MAP), and other risk factors and sepsis-induced AKI in patients presenting to the emergency department (ED). This retrospective study, spanning 1 January 2020, to 30 November 2020, was conducted at a university-affiliated teaching hospital. Patients meeting the Sepsis-2 consensus criteria upon presentation to our ED were categorized into sepsis-induced AKI and non-AKI groups. Clinical parameters (i.e., initial SOFA score and MAP) and laboratory markers (i.e., MDW, RDW, and NLR) were measured upon ED admission. A logistic regression model was developed, with sepsis-induced AKI as the dependent variable and laboratory parameters as independent variables. Three multivariable logistic regression models were constructed. In Model 1, MDW, initial SOFA score, and MAP exhibited significant associations with sepsis-induced AKI (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.668-0.789). In Model 2, RDW, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.712, 95% CI: 0.651-0.774). In Model 3, NLR, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.719, 95% CI: 0.658-0.780). Our novel models, integrating MDW, RDW, and NLR with initial SOFA score and MAP, can assist with the identification of sepsis-induced AKI among patients with sepsis presenting to the ED.