Pyroptosis is considered to play an important role in the occurrence, development and prognosis of septic acute kidney injury (SAKI). We aimed to explore the specific molecular mechanism of S-nitrosoglutathione (SNG) regulating pyroptosis of kidney tubular epithelial cells (KTECs).

By constructing a mice model of sepsis, we pretreated them with SNG and used biochemical methods to detect the levels of serum inflammatory factors and mitochondrial reactive oxygen species (mtROS), assessed the severity of kidney injury and KTECs mitochondrial damage, and detected the expression of KTECs pyroptosis-related proteins and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway proteins.

The kidney injury caused by sepsis was significantly aggravated, and the levels of IL-1β, IL-6, IL-18, TNF-α, malondialdehyde (MDA) and mtROS were all increased, accompanied by the decrease of SIRT3 and SOD2 proteins, while NOD-like receptor with pyrin domain 3 (NLRP3), gasdermin D (GSDMD), Caspase-1 proteins expression and the number of KTECs apoptotic cells were all increased. However, after SNG pretreatment, the levels of IL-1β, IL-6, IL-18, TNF-α, MDA and mtROS were all significantly decreased, the expression of SIRT3 and SOD2 proteins were increased, NLRP3, GSDMD, Caspase-1 proteins expression and the number of KTECs apoptotic cells were decreased.

SNG protects SAKI by regulating the SIRT3/SOD2/mtROS signaling pathway to inhibit the pyroptosis of KTECs.

Methionine sulfoxide reductase A (MsrA) is an important antioxidant enzyme that is present in various tissues and play a crucial role in many pathological processes. However, the role of MsrA in acute kidney injury (AKI) requires further exploration. Here, we aimed to explore whether MsrA is involved in sepsis-associated AKI and the underlying mechanisms. In the present study, AKI was induced by lipopolysaccharide (LPS) in WT mice and MsrA knockout mice. The role of MsrA in LPS-induced injury in the human renal proximal tubule epithelial cell line HK-2 was also examined by MsrA knockdown. MsrA deficiency exacerbated LPS-induced kidney damage in vivo. In addition, MsrA deficiency and silencing intensified iron overload, lipid peroxidation and ferroptosis in LPS-stimulated renal tubular cells. The mechanistic study revealed that MsrA knockout or knockdown led to the oxidation of calcium/calmodulin-dependent protein kinase II (CaMKII) at methionine 281/282, resulting in sustained activation of CaMKII, which upregulated iron metabolism-related proteins such as transferrin receptor 1 (TFR1) by promoting phosphorylation and nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) and induced abnormal iron metabolism. Meanwhile, CaMKII activation downregulated the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) by inhibiting the activity of AMP-activated protein kinase (AMPK) and phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2), resulting in lipid peroxidation. Consequently, LPS-induced ferroptosis was exacerbated. Our study is the first to reveal that MsrA deficiency intensifies LPS-induced ferroptosis through CaMKII activation in renal tubular cells. There are two major mechanisms: one is the promotion of lipid peroxidation by inhibiting the AMPK/NRF2 axis, and the other is abnormal iron metabolism by activating the HIF-1α/TFR1 pathway. MsrA may be a potential therapeutic target for organ and cell damage induced by ferroptosis.

Acute kidney injury (AKI) is a common complication associated with sepsis, yet no effective treatment is currently available. The primary mechanisms involved in lipopolysaccharide (LPS)-induced septic AKI are oxidative stress, inflammation, and apoptosis. This study aimed to investigate the potential renoprotective effects of linagliptin, an antidiabetic dipeptidyl peptidase (DPP)-4 inhibitor, against LPS-induced AKI with special emphasis on renal brain-derived neurotrophic factor (BDNF)/nuclear factor erythroid 2-related factor 2 (NRF2) axis. Mice were divided into control, LPS, LPS + linagliptin, and LPS + linagliptin+ANA-12 (tropomyosin receptor kinase B (TrkB) antagonist) groups. Our results revealed that linagliptin, partially through BDNF augmentation, ameliorated AKI, evidenced by the improved histological structure and function of the kidney where serum creatinine, blood urea nitrogen, cystatin C, and renal kidney injury molecule-1were decreased with increased serum albumin. These improvements result from glucagon-like peptide-1/BDNF/TrkB-mediated NRF2 activation, enhancing antioxidant, anti-inflammatory, and antiapoptotic pathways. Linagliptin, through NRF2 augmentation, suppressed renal myeloperoxidase, malondialdehyde, NLR Family pyrin domain-containing 3 inflammasome, nuclear factor-kappaB, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, B-cell lymphoma 2 (Bcl2)-associated X protein, while boosting the antioxidant glutathione and the antiapoptotic Bcl2 contents. The administration of ANA-12 before linagliptin partially reversed these beneficial effects. Accordingly, our results suggest that linagliptin has therapeutic potential in managing LPS-induced AKI. Furthermore, they provide insights into its underlying mechanisms, highlighting renal BDNF signaling as a potential therapeutic target through downstream NRF2 enhancement and its associated antioxidant, anti-inflammatory, and antiapoptotic effects.

Sepsis, a life-threatening syndrome, results from a dysregulated immune and hemostatic response, contributing to acute lung injury (ALI) and its progression into acute respiratory distress syndrome (ARDS). The development of septic ALI is complex, involving excessive inflammatory mediator production that damages endothelial and epithelial cells, leading to vascular leakage, edema, and vasodilation-key factors in ALI pathogenesis. Long noncoding RNAs (lncRNAs), over 200 nucleotides in length, play critical roles in various biological processes, including sepsis regulation. They exhibit both promotive and inhibitory effects, influencing sepsis progression and resolution. Despite their significance, comprehensive reviews detailing lncRNA involvement in sepsis-induced ALI remain limited. This review aims to address this gap by summarizing the diverse functions of lncRNAs in septic ALI, emphasizing their potential in diagnosis and treatment. Furthermore, we will explore the molecular mechanisms underlying lncRNA involvement, particularly their miRNA-dependent regulatory pathways. Understanding these interactions may provide novel insights into therapeutic strategies for sepsis-induced ALI.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury whose pathogenesis is characterized by excessive lung inflammation and alveolar-capillary barrier permeability. Matrix metalloproteinase 7 (MMP7) can regulate leukocyte recruitment and the production of pro-inflammatory cytokines, but whether it plays a role in acute lung injury (ALI) is an unanswered question. We hypothesized that global loss of MMP7 would attenuate sepsis-induced ALI and systemic inflammation. To test this, male and female MMP7 knockout (MMP7KO) mice and wild-type (WT) littermates were exposed to a two-hit model of ALI (sepsis+hyperoxia). Sepsis was induced through intraperitoneal injection of cecal slurry (CS; 1.6mg/g) or 5% dextrose (control) followed by exposure to hyperoxia (HO; FiO2=0.95) or room air (control, FiO2=0.21). At 24-hours post-CS+HO, we measured weight loss, illness severity, and body temperature. The mice were then sacrificed, and samples from the lungs, kidneys, spleen, blood, peritoneal wash, and bronchoalveolar lavage (BAL) fluid were collected for analysis. Bacterial burden was assessed in the peritoneum, lung, and spleen. Lung inflammation was assessed by BAL inflammatory cell recruitment and pro-inflammatory cytokine concentrations as well as lung tissue mRNA expression of pro-inflammatory cytokines. Alveolar-capillary barrier disruption was quantified by BAL total protein, BAL immunoglobulin M, and lung wet-to-dry weight ratios. Histologic evidence of lung injury was evaluated using a histological scoring system. Systemic inflammation was measured through plasma pro-inflammatory cytokines and peritoneal inflammatory cells. Kidney function, inflammation, and injury were assessed through plasma urea nitrogen concentrations, as well as tissue levels of pro-inflammatory cytokines, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). Relative mRNA expression of MMP-7, MMP-9, and MMP-2 was also quantified in both lung and kidney tissue through qPCR. At 24-hours post-CS+HO all mice developed ALI. Septic mice also had increased systemic inflammation, kidney inflammation, kidney injury, and kidney dysfunction compared to controls. Loss of MMP7 did not affect markers of inflammation, organ injury, or organ dysfunction. Interestingly, septic male mice exhibited more severe illness, systemic and lung inflammation, lung injury, and lung expression of matrix metalloproteinases, while septic female mice exhibited more kidney inflammation, kidney injury, and kidney expression of matrix metalloproteinases. In conclusion, MMP7 is not essential for the development or resolution of sepsis-induced ALI in this model and likely plays a limited role in the condition.

This study aims to investigate the relationship between the triglyceride-glucose (TyG) index in patients with early sepsis-associated acute kidney injury (SA-AKI) and the risk of in-hospital mortality.

Secondary data analysis.

This study analysed secondary data from the Medical Information Mart for Intensive Care (MIMIC) 2008-2022.

A total of 1632 participants were enrolled in the final analysis.

A secondary data analysis study was conducted using data from the MIMIC IV 3.0 database. Participants were divided into four groups based on the quartiles of the TyG index. The primary outcome was all-cause in-hospital mortality. The association between the TyG index and in-hospital mortality among SA-AKI patients was assessed using multivariate COX proportional hazards regression analysis and restricted cubic spline regression analysis. Subgroup and sensitivity analyses were performed to verify the robustness of results.

A total of 1632 patients were included in the study. The in-hospital mortality rate was 31.13%, and the intensive care unit (ICU) mortality rate was 25.25%. Multivariate COX regression analysis showed that the TyG index was independently associated with an increased risk of in-hospital mortality (HR 1.14 (95% CI 1.02 to 1.27); p=0.02) and ICU mortality (HR 1.17; (95% CI 1.04 to 1.32); p=0.01). The restricted cubic spline regression model indicated that the risk of in-hospital and ICU mortality increased linearly with the increase in the TyG index. Sensitivity analysis demonstrated that the effect size and direction were consistent across different subgroups, and the results were stable.

A high TyG index is associated with increased mortality during hospitalisation in patients with SA-AKI. Larger-scale prospective studies are needed to confirm these findings.

In recent years, lactylation, a novel post-translational modification, has demonstrated a unique role in bridging cellular metabolism and epigenetic regulation. This modification exerts a dual-edged effect in both cancer and non-cancer diseases by dynamically integrating the supply of metabolic substrates and the activity of modifying enzymes: on one hand, it promotes tissue homeostasis and repair through the activation of repair genes; on the other, it exacerbates pathological progression by driving malignant phenotypes. In the field of oncology, lactylation regulates key processes such as metabolic reprogramming, immune evasion, and therapeutic resistance, thereby shaping the heterogeneity of the tumor microenvironment. In non-cancerous diseases, including neurodegeneration and cardiovascular disorders, its aberrant activation can lead to mitochondrial dysfunction, fibrosis, and chronic inflammation. Existing studies have revealed a dynamic regulatory network formed by the cooperation of modifying and demodifying enzymes, and have identified mechanisms such as subcellular localization and RNA metabolism intervention that influence disease progression. Nevertheless, several challenges remain in the field. This article comprehensively summarizes the disease-specific regulatory mechanisms of lactylation, with the aim of providing a theoretical foundation for its targeted therapeutic application.

Today, acute kidney injury (AKI) caused by sepsis, with its high incidence and rising mortality, is becoming a global problem. Many previous studies have proved that NLRP3 is a critical role in NLRP3 inflammasome activation to regulate inflammatory responses in a variety of diseases including AKI. Our study is aimed to explore the role and upstream regulatory mechanism of NLRP3 in AKI. In this study, we demonstrated that LPS treatment induced the upregulation of NLRP3 in HK-2 cells. Functionally, NLRP3 knockdown inhibited cell apoptosis, inflammatory response and NLRP3 inflammasome activation. Mechanistically, OIP5-AS1 competitively bound with miR-186-5p to promote NLRP3 level, and further activate TLR4/NF-κB signaling. Additionally, OIP5-AS1 was negatively associated with miR-186-5p but positively correlated with NLRP3 in rat renal tissues. The rescue assays suggested that NLRP3 reversed the effects of silencing OIP5-AS1 on cell apoptosis and inflammatory response. At last, OIP5-AS1 aggravated renal injury and inflammation in vivo. All findings indicated that the OIP5-AS1 contributed to sepsis-induced AKI by promoting NLRP3 inflammasome activation via miR-186-5p/NLRP3 axis. OIP5-AS1 could serve as a potential diagnostic and therapeutic marker in sepsis-induced AKI.

Persistent sepsis-associated acute kidney injury (SA-AKI) shows poor clinical outcomes and remains a therapeutic challenge for clinicians. Early identification and prediction of persistent SA-AKI are crucial.

The aim of this study was to develop and validate an interpretable machine learning (ML) model that predicts persistent SA-AKI and to compare its diagnostic performance with that of C-C motif chemokine ligand 14 (CCL14) in a prospective cohort.

The study used 4 retrospective cohorts and 1 prospective cohort for model derivation and validation. The derivation cohort used the MIMIC-IV database, which was randomly split into 2 parts (80% for model construction and 20% for internal validation). External validation was conducted using subsets of the MIMIC-III dataset and e-ICU dataset, and retrospective cohorts from the intensive care unit (ICU) of Northern Jiangsu People's Hospital. Prospective data from the same ICU were used for validation and comparison with urinary CCL14 biomarker measurements. Acute kidney injury (AKI) was defined based on serum creatinine and urine output, using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Routine clinical data within the first 24 hours of ICU admission were collected, and 8 ML algorithms were used to construct the prediction model. Multiple evaluation metrics, including area under the receiver operating characteristic curve (AUC), were used to compare predictive performance. Feature importance was ranked using Shapley Additive Explanations (SHAP), and the final model was explained accordingly. In addition, the model was developed into a web-based application using the Streamlit framework to facilitate its clinical application.

A total of 46,097 patients with sepsis from multiple cohorts were enrolled for analysis. Among 17,928 patients with sepsis in the derivation cohort, 8081 patients (45.1%) showed progression to persistent SA-AKI. Among the 8 ML models, the gradient boosting machine (GBM) model demonstrated superior discriminative ability. Following feature importance ranking, a final interpretable GBM model comprising 12 features (AKI stage, ΔCreatinine, urine output, furosemide dose, BMI, Sequential Organ Failure Assessment score, kidney replacement therapy, mechanical ventilation, lactate, blood urea nitrogen, prothrombin time, and age) was established. The final model accurately predicted the occurrence of persistent SA-AKI in both internal (AUC=0.870) and external validation cohorts (MIMIC-III subset: AUC=0.891; e-ICU dataset: AUC=0.932; Northern Jiangsu People's Hospital retrospective cohort: AUC=0.983). In the prospective cohort, the GBM model outperformed urinary CCL14 in predicting persistent SA-AKI (GBM AUC=0.852 vs CCL14 AUC=0.821). The model has been transformed into an online clinical tool to facilitate its application in clinical settings.

The interpretable GBM model was shown to successfully and accurately predict the occurrence of persistent SA-AKI, demonstrating good predictive ability in both internal and external validation cohorts. Furthermore, the model was demonstrated to outperform the biomarker CCL14 in prospective cohort validation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can result from various factors, including sepsis, one of the high-risk causes of ALI/ARDS. Recent research emphasizes the role of Glutamate metabolism in ALI/ARDS. Our study found a strong correlation between the difference in serological Glutamate levels of arterial vs venous blood and the progression of lung injury. High arterial - venous (A-V) Glutamate discrepancies were significantly associated with severity in ALI/ARDS patients. Additionally, the subunit of Glutamate transporter system XC- was notably elevated in mouse lungs affected by sepsis and LPS-induced macrophages. Pharmacological inhibition of system XC- or knocking down xCT worsened sepsis-related lung injury in mice. We also showed that xCT in macrophages is essential for activating system XC- for Glutamate transport, offering protection against sepsis-related ALI. Our findings highlight the therapeutic potential of Glutamate transport in mitigating lung injury and provide a promising approach for predicting ALI/ARDS prognosis.

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.

Combination therapy with a beta-lactam and an aminoglycoside is currently recommended for the empirical treatment of urosepsis. Nephrotoxicity is the most common adverse effect of aminoglycosides and acute kidney injury (AKI) has a significant prognostic impact in septic shock. This study aimed to evaluate the impact of empirical antibiotic therapy with or without an aminoglycoside on survival and renal outcomes in patients admitted to the intensive care unit (ICU) with urosepsis.

This multicenter, retrospective, comparative study included all adults admitted to the ICU for urinary sepsis or septic shock between January 2015 and May 2022 in four ICUs of three university hospitals within the Assistance Publique-Hôpitaux de Paris (APHP). The primary outcome was mortality on day 30 after ICU admission. Secondary endpoints included the lack of renal recovery, the need for new renal replacement therapy (RRT), the Major Adverse Kidney Events at day 30 (MAKE 30) and ICU length of stay. Confounding by indication was taken into account using propensity score weighting.

A total of 580 patients were included, median age was 69 years (interquartile: 58-77) and 53.6% were male. Overall, 335 patients (57.8%) were in septic shock and 448 (79.2%) had AKI on admission. A total of 579 patients (99.8%) received a beta-lactam as empirical therapy (with (n = 444) or without (n = 136) aminoglycosides). The overall 30-day mortality rate was 10.5% (61/580). After propensity score weighting, the mortality rate in patients receiving aminoglycosides was 7.7% (7/91) compared to 12.1% (11/91) in those not receiving aminoglycosides (adjusted hazard ratio (aHR) = 0.65 [0.35; 1.23], p = 0.19). No significant differences were found in the lack of renal recovery at day 30 (aHR = 0.88 [0.49; 1.58], p = 0.67), the need for new RRT within 30 days (aHR = 1.01 [0.54; 1.88], p = 0.97), MAKE 30 (aHR = 0.94 [0.60; 1.50], p = 0.81), and ICU length of stay among survivors (aHR = 1.07 [0.87; 1.31], p = 0.53).

Including aminoglycosides in the empirical antibiotic therapy did not significantly improve 30-day survival in patients admitted to the ICU for urosepsis. However, the use of aminoglycosides was not associated with worse renal outcomes.

Sepsis, a medical emergency with high mortality rates, demands comprehensive care spanning from early identification to patient rehabilitation. The sepsis survival chain encompasses early recognition, severity assessment, activation of emergency services, initial antimicrobial therapy, hemodynamic stabilization, and integrated rehabilitation. These interconnected steps are critical to reducing morbidity and mortality. Despite advancements in international guidelines, adherence remains limited, contributing to a significant disease burden. Beyond its acute phase, post-sepsis syndrome (PSS) is characterized by long-term immune dysregulation, chronic inflammation, and metabolic dysfunction, predisposing survivors to recurrent infections, cardiovascular disease, and neurocognitive decline. Mitochondrial dysfunction and epigenetic modifications play a central role in prolonged immunosuppression, impairing adaptive and innate immune responses. Sepsis-induced organ dysfunction impacts multiple systems, including the brain, heart, and kidneys. In the brain, it is associated with neuroinflammation, blood-brain barrier dysfunction, and the accumulation of neurotoxic proteins, leading to acute and chronic cognitive impairment. Myocardial dysfunction involves inflammatory mediators such as TNF-α and IL-6, while sepsis-associated acute kidney injury (SA-AKI) arises from hypoperfusion and inflammation, heightening the risk of progression to chronic kidney disease. Additionally, immune alterations such as neutrophil dysfunction, continuous platelet activation, and suppressed antitumoral responses contribute to increased infection risk and long-term complications. Timely and targeted interventions, including antimicrobial therapy, cytokine modulation, immune restoration, metabolic support, and structured rehabilitation strategies, are pivotal for improving outcomes. However, financial and infrastructural limitations in low-resource settings pose significant barriers to effective sepsis management. Precision medicine, AI-driven early warning systems, and optimized referral networks can enhance early detection and personalized treatments. Promoting public and professional awareness of sepsis, strengthening multidisciplinary post-sepsis care, and integrating long-term follow-up programs are imperative priorities for reducing mortality and improving the quality of life in sepsis survivors.

Sepsis-induced acute kidney injury (S-AKI) is a common complication of sepsis. It occurs at high incidence and is associated with a high level of mortality in the intensive care unit (ICU). The pathophysiologic mechanisms underlying S-AKI are complex, and include renal vascular endothelial cell dysfunction. The endothelial glycocalyx (EG) is a polysaccharide/protein complex located on the cell membrane at the luminal surface of vascular endothelial cells that has anti-inflammatory, anti-thrombotic, and endothelial protective effects. Recent studies have shown that glycocalyx damage plays a causal role in S-AKI progression. In this review, we first describe the structure, location, and basic function of the EG. Second, we analyze the underlying mechanisms of EG degradation in sepsis and S-AKI. Finally, we provide a summary of the potential therapeutic strategies that target the EG.

Abstract-This study explored the role of the non-canonical STING-PERK signaling pathway in sepsis-associated acute kidney injury (SA-AKI). Gene expression data from the GEO database and serum STING protein levels in patients with SA-AKI were analyzed. An LPS-induced mouse model and an in vitro model using HK-2 cells were used to investigate the role of STING in SA-AKI. STING expression was suppressed using shRNA silencing technology and the STING inhibitor C176. Kidney function, inflammatory markers, apoptosis, and senescence were measured. The role of the STING-PERK pathway was investigated by silencing PERK in HK-2 cells and administering the PERK inhibitor GSK2606414. STING mRNA expression and serum STING protein levels were significantly higher in patients with SA-AKI. Suppressing STING expression improved kidney function, reduced inflammation, and inhibited apoptosis and senescence. Silencing PERK or administering GSK2606414 suppressed the inflammatory response, cell apoptosis, and senescence, suggesting that PERK is a downstream effector in the STING signaling pathway. The STING-PERK signaling pathway exacerbates cell senescence and apoptosis in SA-AKI. Inhibiting this pathway could provide potential therapeutic targets for SA-AKI treatment.

Urine-derived stem cells (USCs) are adult human stem cells that can be collected noninvasively from urine and cultured in vitro. Because of their renal origin and reported therapeutic effects, we hypothesized that USCs would home to the injured kidney in acute kidney injury (AKI) models. We used mouse models of glycerol-induced rhabdomyolysis or unilateral nephrectomy with clamping ischemia reperfusion injury to model AKI. To track USC homing by live animal imaging, we administered luciferase-expressing (Luc) USCs to mice by intraperitoneal injection. We observed USC localization to both the tubules and glomeruli of injured mice within 3 h by histology. We confirmed the presence of Luc-USCs in the kidney at 3 h, 24 h, and 48 h after the injection using biodistribution analysis of quantitative bioluminescence tomography imaging. We performed immunostaining for kidney injury molecule-1 (KIM-1/HAVCR1/TIM-1) for kidney injury and found reduced expression in USC-treated group at 24 h after injection. To evaluate the effects of the human USCs on injured human nephrons, we injured human kidney organoids with the nephrotoxin cisplatin (5 μM) followed by 5 × 104 USC treatment. USCs were incorporated and lowered expression of KIM-1 in the organoids. USCs home to injured nephrons and reduce measures of kidney injury.

Sepsis-associated kidney injury (SAKI) is a prevalent complication in intensive care unit (ICU) patients with sepsis. Diagnosis currently relies on clinical assessment, urine output, and serum creatinine levels, yet effective clinical treatments remain scarce. Our objectives are to explore prospective, targeted medications for the treatment of septic kidney injury and to employ bioinformatics to identify key genes and pathways that may be implicated in the pathogenesis of SAKI.

We utilized the GEO database for differential gene screening. Related genes of septic kidney injury were identified through Pubmed2Ensembl, followed by annotation and visualization of gene ontology biological processes and KEGG pathways using DAVID. Protein-protein interactions were analyzed with the STRING database, and hub genes were identified using Cytoscape software. Candidate genes were further validated through Metascape. The CTD database was employed to uncover the relationship between hub genes and acute kidney injury (AKI). CIBERSORT was applied to evaluate the infiltration of immune cells and their association with hub genes. Hub genes were experimentally verified through qPCR detection. Lastly, the Drug-Gene Interaction Database (DGIdb) was utilized to identify drug-gene interactions.

Six genes, including TNF, CXCL8, IL-6, IL-1β, IL-2, and IL-10, were associated with three major signaling pathways: the COVID-19 adverse outcome pathway, an overview of pro-inflammatory and pro-fibrotic mediators, and the interleukin-10 signaling pathway. Additionally, 12 targeted drugs were identified as potential therapeutic agents.

It is clinically relevant to predict outcomes in dogs with acute kidney injury (AKI) treated with haemodialysis. The aim of this study was to evaluate the prognostic value of contrast-enhanced ultrasound (CEUS) and its role in discriminating between AKI and acute impairment associated with chronic kidney disease (AKI/CKD).

Dogs diagnosed with AKI or AKI/CKD were prospectively enrolled in the study. For all dogs, CEUS was performed at admission (T0). In addition, in haemodialysis-treated dogs, it was performed after the first dialysis (T1) and 7 days (T7) and 30 days (T30) after admission.

A total of 41 dogs were enrolled, of which 30 were treated with haemodialysis and 11 received medical therapy. No significant difference was found between CEUS values at T0 in surviving and non-surviving patients after haemodialysis. A significant difference in cortical peak enhancement intensity (PI) values was found between T0, T1, T7 and T30, with the highest PI value at T0, a significant reduction at T1 and a progressive reduction in subsequent checks. There were no significant differences in CEUS parameters at T0 between patients with AKI and AKI/CKD.

AKI aetiology was unknown in most cases, which limits the generalisability of the findings. Furthermore, the small sample size means that the statistical analysis is likely underpowered.

CEUS could be helpful in evaluating of the prognosis of dogs with AKI during haemodialysis.

Sepsis-induced acute kidney injury (AKI) is a severe condition characterized by dysregulation of pro- and anti-inflammatory responses. Targeting macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 cells offers a potential therapeutic approach for AKI. Trametinib (TRAM), an inhibitor of the MEK1/2 signaling pathway, was evaluated for its impact on M1/M2 polarization in AKI.

Wild-type (WT) mice were subjected to lipopolysaccharide (LPS)-induced AKI and intraperitoneally treated with dimethyl sulfoxide (DMSO) or TRAM (10 mg/kg) for three days. Renal function was assessed by measuring creatinine levels. While histopathological changes, RNA sequencing data, and serum cytokine levels were analyzed. Macrophage M1/M2 polarization in kidney tissues was examined using flow cytometry and immunohistochemistry. Murine bone marrow-derived macrophages (BMDMs) were polarized to the M1 or M2 phenotype in vivo and treated with or without TRAM (10 μM). M1/M2 polarization was analyzed via flow cytometry, and PI3K/Akt signaling was evaluated by western blotting.

TRAM significantly improved renal function, as demonstrated by reduced serum creatinine levels (p < 0.01) and ameliorated histopathological damage (p < 0.01). Flow cytometry and immunohistochemistry revealed that TRAM markedly inhibited pro-inflammatory M1 macrophage polarization (p < 0.001). Additionally, TRAM reduced serum level of IFN-γ (p < 0.01) and IL-17 (p < 0.001). In vitro, TRAM suppressed M1 polarization (p < 0.05) by inhibiting the PI3K/Akt signaling pathway.

TRAM mitigated LPS-induced AKI by suppressing M1 macrophage polarization via the PI3K/Akt pathway, highlighting its therapeutic potential for AKI and other inflammatory kidney diseases.

Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Due to the high mortality rates and treatment costs associated with sepsis, research is focusing on innovative treatment strategies to replace one dimensional approaches. Recent studies are being conducted on the use of immunotherapeutics in sepsis and the impact of treatment timing. This study aimed to elucidate the significance of treatment timing in sepsis immunotherapy with Tocilizumab (TCZ) and the implications of differences in treatment timing.

LPS-induced sepsis model was established in rats to assess the changes in interleukin-6 (IL-6) over a 24-h sepsis period and its correlation with lung and kidney injury. The impact of TCZ treatments at various time points was evaluated by molecular and histopathological methods. The effect of TCZ treatment timing on survival was analyzed using Kaplan-Meier survival analysis.

IL-6 reached peak concentrations in the early stages of sepsis, whereas lung damage peaked subsequent to the IL-6 peak, and kidney damage manifested considerably later. The early treatment group, receiving intervention one hour post-sepsis induction, exhibited the most favorable molecular and histopathological outcomes. Conversely, the group receiving the latest treatment, at sixteen hours post-sepsis induction, demonstrated the poorest results. Survival analysis indicated that the group treated at the tenth hour exhibited the highest survival rate.

Variations in the timing of sepsis treatment with TCZ yield significantly different molecular outcomes, histopathological results, and survival rates. A thorough investigation of the timing of immunotherapeutic applications in sepsis treatment will enhance the efficiency of sepsis treatments.

The purpose of this study was to develop a straightforward, easy-to-use online dynamic nomogram for the identification of children who are at high risk of developing acute kidney injury (AKI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

This was a two-center study in which 242 children in Henan Provincial Children's Hospital composed the training cohort, and 115 children in the First Affiliated Hospital of Zhengzhou University composed the validation cohort. Kaplan-Meier survival analysis was used to compare survival between children with nonacute kidney injury (NAKI) and children with AKI. Multivariate logistic regression analysis was used to identify risk factors for AKI in children who underwent HSCT. The selected variables were utilized to construct nomograms, which were validated via the concordance index (C-index), decision curve analysis, calibration curve analysis, and receiver operating characteristic (ROC) curve analysis.

Cumulative survival was significantly lower in children with AKI than in children without kidney injury (p < 0.01). Eight variables were included in the nomogram: hepatic veno-occlusive disease (HVOD), graft-versus-host disease (GVHD), ferritin, C-reactive protein (CRP), Cytomegalovirus infection (CMV), thrombotic microangiopathy (TMA), human leukocyte antigen (HLA), and nephrotoxic drugs. The nomogram calibration curves in the training and validation cohorts were highly comparable to the standard curves. The areas under the curve (AUCs) of the prediction model were 0.963 and 0.910 in the training cohort and validation cohort, respectively. The decision curve analysis (DCA) revealed that the model had a significant clinical benefit.

The occurrence of AKI affects the prognosis of children who undergo HSCT. We developed a dynamic online nomogram for predicting AKI in children who underwent allo-HSCT on the basis of eight variables. The predictive value and clinical benefit of the nomogram model were acceptable.

Developing and validating a simple and clinically useful dynamic nomogram for predicting early acute kidney injury (AKI) in patients with acute heart failure (AHF) admitted to the intensive care unit (ICU).

Clinical data from patients with AHF were obtained from the Medical Information Mart for Intensive Care IV database. The patients with AHF were randomly allocated into derivation and validation sets. The independent predictors for AKI development in AHF patients were identified through least absolute shrinkage and selection operator and multivariate logistic regression analyses. A nomogram was developed based on the results of the multivariable logistic regression to predict early AKI onset in AHF patients, which was subsequently implemented as a web-based calculator for clinical application. An evaluation of the nomogram was conducted using discrimination, calibration curves, and decision curve analyses (DCA).

After strict screening, 1,338 patients with AHF were included in the derivation set, and 3,129 in the validation set. Sepsis, use of human albumin, age, mechanical ventilation, aminoglycoside administration, and serum creatinine levels were identified as predictive factors for AKI in patients with AHF. The discrimination of the nomogram in both the derivation and validation sets was 0.81 (95% confidence interval: 0.78-0.83) and 0.79 (95% confidence interval: 0.76-0.83). Additionally, the calibration curve demonstrated that the predicted outcomes aligned well with the actual observations. Ultimately, the DCA curves indicated that the nomogram exhibited favorable clinical applicability.

The nomogram that integrates clinical risk factors and enables the personalized prediction of AKI in patients with AHF upon admission to the ICU, which has the potential to assist in identifying AHF patients who would derive the greatest benefit from interventions aimed at preventing and treating AKI.

Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and is associated with high mortality. Therefore, early recognition of SA-AKI is essential for administering supportive treatment and preventing further damage. This study aimed to identify and validate metabolite biomarkers of SA-AKI to assist in early clinical diagnosis.

Untargeted renal proteomic and metabolomic analyses were performed on the renal tissues of LPS-induced SA-AKI and sepsis mice. Glomerular filtration rate (GFR) monitoring technology was used to evaluate real-time renal function in mice. To elucidate the distinctive characteristics of SA-AKI, a multi-omics Spearman correlation network was constructed integrating core metabolites, proteins, and renal function. Subsequently, metabolomics analysis was used to explore the dynamic changes of core metabolites in the serum of SA-AKI mice at 0, 8, and 24 h. Finally, a clinical cohort (28 patients with SA-AKI vs. 28 patients with sepsis) serum quantitative metabolomic analysis was carried out to build a diagnostic model for SA-AKI via logistic regression (LR).

Thirteen differential renal metabolites and 112 differential renal proteins were identified through a multi-omics study of SA-AKI mice. Subsequently, a multi-omics correlation network was constructed to highlight five core metabolites, i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, creatine, myristic acid, and inosine, the early changes of which were then observed via serum time series experiments of SA-AKI mice. The levels of 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, and creatine increased significantly at 24 h, myristic acid increased at 8 h, while inosine decreased at 8 h. Ultimately, based on the identified core metabolites, we recruited 56 patients and constructed a diagnostic model named IC3, using inosine, creatine, and 3-hydroxybutyric acid, to early identify SA-AKI (AUC = 0.90).

We proposed a blood metabolite model consisting of inosine, creatine, and 3-hydroxybutyric acid for the early screening of SA-AKI. Future studies will observe the performance of these metabolites in other clinical populations to evaluate their diagnostic role.

This study explores alterations in renal cortical perfusion post-Early Goal-Directed Therapy (EGDT) in sepsis patients, to investigate its association with major adverse kidney events within 30 days (MAKE-30) and identify hemodynamic factors associated with renal cortical perfusion.

Sepsis patients admitted to the ICU from Jan 2022 to Jul 2023 were prospectively enrolled. Contrast-enhanced ultrasound (CEUS) assessed renal cortical perfusion post-EGDT. Hemodynamic parameters and renal resistive index (RRI) were collected. Patients were categorized into MAKE-30 and non-MAKE-30 groups. The study examined the association between renal cortical perfusion and MAKE-30, explored the hemodynamic factors related to renal cortical perfusion.

Of 94 sepsis patients, 46 (48.9 %) experienced MAKE-30. Distinctions in pulmonary (P = 0.012) and abdominal infection sites (P = 0.001) and significant SOFA (P < 0.001) and APACHE II scores (P = 0.003) differences were observed. No significant differences in baseline characteristics, vasopressor, or diuretic doses were noted (P > 0.05). Hemodynamic parameters in MAKE-30 and non-MAKE-30 patients showed no significant differences. RRI was higher in MAKE-30 patients (0.71 vs 0.66 P = 0.005). Renal microcirculation parameters, including AUC (p = 0.035), rBV (p = 0.021), and PI (p = 0.003), were lower in MAKE-30. Reduced cortical renal perfusion was associated with an increased risk of MAKE-30. Renal cortical perfusion RT was identified as an independent factor associated with this risk (HR 2.278, 95 % CI (1.152-4.507), P = 0.018). RRI correlated with renal cortical perfusion AUC (r = -0.220 p 0.033).

Despite normal systemic hemodynamics post-sepsis EGDT, MAKE-30 patients show reduced renal cortical perfusion. CEUS-derived RT is an independent factor associated with this change. RRI correlates with renal cortical perfusion.

Periprosthetic joint infections (PJIs) are a significant complication following total hip arthroplasty, impacting patient health and healthcare costs. This study examines the incidence of acute kidney injury (AKI) in patients undergoing hip PJI treatment with a combination of intravenous and intra-articular antibiotic infusion therapies.

A retrospective review of 151 patient records from May 1, 2010 to December 30, 2022 was conducted at a single academic hospital. Patients were treated for hip PJIs using debridement, antibiotics, and implant retention or single-stage revision surgeries. AKI was classified according to the Kidney Disease: Improving Global Outcomes criteria.

Among 151 patients, 17 (11.26%) developed AKI, with 13 cases resolving transiently before discharge. The median onset of AKI was on postoperative day 2, with stage I AKI being the most prevalent, accounting for 64.71% of cases. Diabetes and low baseline serum creatinine levels were identified as independent risk factors for AKI, with odds ratios of 9.69 and 1.09, respectively.

The combined regimen of intra-articular and intravenous antibiotic infusion appears to have a manageable risk profile regarding AKI. This approach could serve as a viable alternative for PJI management, emphasizing the importance of careful patient monitoring and tailored antibiotic regimens. Further studies are recommended to optimize treatment protocols and mitigate risks.

The influence of disease-causing pathogen on acute kidney injury (AKI) in septic patients is poorly understood.

We examined the association of microbial pathogen with AKI among patients with community-onset sepsis.

This was a retrospective cohort study. Patient data were acquired from the nationwide multicenter PINC AI Healthcare Database (2016-2020). Participants included adult patients with Centers for Disease Control and Prevention-defined community-onset sepsis.

The primary exposure was pathogen type identified by culture growth. Microbial cultures from any site were included. The primary endpoint was development of AKI within 7 days of admission using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. We used multilevel logistic regression to examine the association between pathogen type and AKI. Escherichia coli-positive cultures were used as the reference category.

We included 119,733 patients with community-onset sepsis. The median age was 67 years, 33.3% were mechanically ventilated, 36.1% received vasopressors, and hospital mortality was 13.1%. Forty-two thousand twenty-seven patients (35.1%) developed stage 1 AKI, 22,979 (19.2%) developed stage 2 AKI, and 25,073 (20.9%) developed stage 3 AKI. Relative to patients with E. coli infection (odds ratio [OR], 1.0), Proteus species (OR, 1.26; 95% CI, 1.06-1.50), and Streptococcus species (OR, 1.24; 95% CI, 1.10-1.41) were associated with increased odds of AKI. Meanwhile, Pseudomonas aeruginosa (OR, 0.56; 95% CI, 0.49-0.64) and Serratia species (OR, 0.70; 95% CI, 0.52-0.94) were associated with decreased odds of AKI.

The causative pathogen in patients with sepsis may influence the development of AKI. Further mechanistic and clinical research is needed to confirm these findings and to explore how different pathogens may affect AKI risk in critically ill patients.

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 is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt4+ and honokiol (HK) by the chelation, π-π conjugation, hydrophobic action, and the surfactant properties of Tween-80. These nanomicelles not only enhance drug bioavailability (encapsulation rates: Pt─49%, HK─70%) and reduce drug toxicity (safety dose: <20 μg/g) but also improve targeting toward damaged renal tissues. Furthermore, Pt4+ and HK in the nanomicelles exert a synergistic physiological effect by scavenging free radicals to alleviate oxidative damage, inhibiting macrophage activation and the release of inflammatory factors to regulate inflammation, and displaying broad-spectrum antimicrobial activity to control infection. These actions collectively protect renal tissue and restore its functionality. Here, we constructed metal-polyphenol nanomicelles (Pt/HK-NMs) via ingenious and efficient self-assembly, providing a new strategy to compensate for deficiencies in the hemodialysis and antibiotic treatment of SAKI.

Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe. We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day 7 as secondary outcome. Results: Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, hazard ratio = 0.75, 95% CI [0.52-1.08], P = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, hazard ratio = 0.57, 95% CI [0.36-0.91], P = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (P < 0.001) and had more days alive and free from RRT (P < 0.001). Conclusions: Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.

In recent years, ferroptosis has been found to play an important role in various acute kidney injury (AKI). However, relatively little research has been conducted on sepsis-induced acute kidney injury (SI-AKI). As an important trigger of ferroptosis, how mitochondrial damage plays a regulatory role in SI-AKI is still unclear. To explore the potential relationship between mitochondria and ferroptosis, we established a SI-AKI rat model by intraperitoneal injection of lipopolysaccharide (LPS). Transcriptome sequencing was used to detect changes in gene transcription levels in the control group, LPS 3 h group, LPS 6 h group and LPS 12 h group. The severity of kidney injury was determined based on serum creatinine (CRE), blood urea nitrogen (BUN), tissue HE staining, TUNEL staining and inflammatory factor levels. Cytoscape software was utilized to screen several mitochondria-related HUB genes, and NADH dehydrogenase [ubiquinone] ferrithionein 3 (NDUFS3) was selected for subsequent validation due to its novelty and feasibility. qRT-PCR, Western blot was employed to evaluate the expression of NDUFS3 in kidney tissues. GO enrichment analysis revealed that up-regulated genes in the LPS 12 h group were enriched in several cell death terms while down-regulated genes were enriched in lipid metabolic process and oxidation-reduction progress terms. Furthermore, Western blot, IHC, MDA, GSH and iron content levels were used to assess ferroptosis in the kidney tissue of the SI-AKI rats, dihydroethidium (DHE) assay and ATP kit were used to assess mitochondrial ROS levels and mitochondrial function. To further validate the function of NDUFS3, we constructed overexpression rats using hydrodynamic method by tail vein injection of pc DNA3.1-NDUFS3 overexpression plasmid. we utilized LPS to stimulate HK-2 cells and establish an in vitro model. We then overexpressed NDUFS3 using pcDNA 3.1. The overexpression of NDUFS3 was found to inhibit LPS-induced ferroptosis and mitochondrial damage in HK-2 cells, as evidenced by Western blot, MDA, GSH, divalent iron, ROS levels, Mitosox red, ATP content and transmission electron microscopy. Finally, the use of Compound C to inhibit AMPK in HK-2 cells demonstrated that NDUFS3 plays a protective role through the AMPK pathway. Therefore, our study supports the emerging role of NDUFS3 in SI-AKI, providing new potential mitochondria-related targets for the treatment of SI-AKI.

Sepsis, a life-threatening condition characterized by dysregulated host responses to infection, often leads to multi-organ dysfunction, including kidney injury. Kidney damage in sepsis can have severe consequences and is associated with high mortality rates. This study aimed to investigate the potential therapeutic effects of fosfomycin (FOS), a broad-spectrum antibiotic with immunomodulatory properties, on kidney damage induced by cecal ligation and puncture (CLP)-induced sepsis in a rodent model. In total, 24 rats were randomly divided into three groups. Group 1 (n = 8), the healthy control group (C), received a single dose of 0.9% NaCl (saline) solution via an intraperitoneal (i.p.) route. To group 2 (n = 8), the CLP group, CLP-induced sepsis was applied without medication, and a single dose of 0.9% NaCl (saline) solution was applied i.p. before induction. To group 3 (n = 8), the CLP + FOS (500 mg/kg) group, a single dose of 500 mg/kg FOS was administered i.p. before sepsis induction. The effects of fosfomycin on kidney function, histopathological changes, inflammatory markers, oxidative stress, and apoptosis were assessed. In the fosfomycin-treated group, the histological analysis results demonstrated reduction in kidney tissue damage and inflammation. Additionally, fosfomycin attenuated the upregulation of pro-inflammatory cytokines and reduced oxidative stress markers in kidney tissue. Furthermore, fosfomycin treatment was associated with a decrease in apoptotic cell death in the kidney. These findings suggest that fosfomycin may have a protective effect on kidney damage caused by CLP-induced sepsis. The potential mechanisms underlying this protection include the modulation of inflammation, reduction of oxidative stress, and inhibition of apoptosis.

We assessed the predictive value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in predicting the onset of acute kidney injury (AKI) in sepsis patients in the intensive care unit (ICU).

In this retrospective analysis, we examined the medical records of sepsis patients admitted to the ICU. After ICU admission, blood samples were taken at 0 h, 6 h, 12 h, 24 h, and 48 h. Using an enzyme-linked immunosorbent assay, the concentrations of serum creatinine, NGAL, and IL-18 were determined.

This study comprised a total of 197 participants, 104 of whom had AKI and 93 of whom did not. Blood concentrations of NGAL and IL-18 increased prior to serum creatinine levels. Between 6-48 hours after ICU administration, NGAL and IL-18 levels in the AKI group were considerably higher than those in the non-AKI group, and creatinine levels between the two groups were significantly different after 48 hours. Based on receiver operating characteristic (ROC) curve analysis, the area under the curve of NGAL and IL-18 for predicting AKI was 0.781 and 0.883, respectively.

Blood NGAL and IL-18 are potential biomarkers for the early prediction of AKI in sepsis patients in the ICU.

Background: Renal replacement therapy with an oXiris hemofilter may be helpful for patients with acute kidney injury in conjunction with sepsis and septic shock. The aim of this study was to assess the impact of an oXiris membrane on septic shock patients. Methods: All renal replacement therapies with oXiris (Baxter, Deerfield, IL, USA) performed between January 2018 and August 2021 were retrospectively analyzed. CRRT was initiated in continuous venovenous hemodiafiltration (CVVHDF) mode using Prismaflex System (Baxter). Demographic data, starting point of infection, source control, etiology, and course of treatment were analyzed. Results: A total of 32 patients were included in the study. Most patients treated with oXiris had acute kidney injury (AKI) and required CRRT. One patient had KDIGO 1 AKI (3.1%), three patients (9.4%) had KDIGO 2 AKI, and 28 patients (87.5%) had KDIGO 3 AKI. A statistically significant decrease in vasopressin dosage was required to achieve adequate MAP after 24 and 72 h, and a statistically significant decrease in norepinephrine dosage after 72 h was observed, with no SOFA score change on days 2 and 3. Procalcitonin and lactate levels did not change after 24 and 72 h. No beneficial effect on mortality was observed. Conclusions: Treatment with an oXiris membrane can positively impact vasopressors' requirement but not influence SOFA score, procalcitonin or lactate levels, or mortality in septic shock patients.

To investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI).

We performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days.

During the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99).

The administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.

Acute kidney injury (AKI) is commonly encountered in critical care medicine as is intravenous fluid therapy. It is accepted that there is interplay between fluid use and AKI, both potentially positive and negative. An understanding of the physiological rationale for fluid is important to help clinicians when considering fluid therapy in patients with, or at risk for AKI; this includes understanding choice of fluid, method of monitoring, administration and clinical sequelae.

There is increasing interest in combining both static and dynamic measures to assess fluid balance, fluid responsiveness effects of fluid therapy, which are areas requiring ongoing study to translate this theory into clinically useful practice at the bedside. Whilst the debate of choice of crystalloid in ICU practice continues, further evidence for benefits for balanced solutions emerges in the form of international guidelines and patient data meta-analysis of previously performed trials.

This review assesses the physiological rationale for fluid use in ICU cohorts with AKI of various types, as well as a systematic approach for choice of fluid therapy using a number of different variables, which aims to help guide clinicians in managing fluid use and fluid balance in critically ill patients with AKI.

Sepsis-associated acute kidney injury (S-AKI) is a critical complication that significantly contributes to the morbidity and mortality of sepsis patients. This narrative review explores the complex and multifactorial pathophysiology of S-AKI, which involves hemodynamic alterations, microcirculatory dysfunction, endothelial damage, inflammatory responses, oxidative stress, and direct tubular injury. Conventional perspectives linking S-AKI primarily to reduced renal blood flow are now being reconsidered, with growing insights highlighting the significance of microcirculatory dysfunction and endothelial activation as key contributors. The review also discusses the current diagnostic approaches for S-AKI, emphasizing the limitations of existing biomarkers and the need for earlier and more accurate detection methods. Standard treatment strategies focus on supportive care, including fluid management, vasopressor therapy, and renal replacement therapy. However, these approaches often fail to address the underlying mechanisms of S-AKI, resulting in persistently high mortality rates. Emerging therapies, including the use of antioxidants, anti-inflammatory agents, and stem cell-based treatments, offer the potential for improved outcomes. These innovative approaches aim to target the pathophysiological processes at the molecular level, offering hope for better management of S-AKI. The review highlights the need for ongoing research to further understand the mechanisms driving S-AKI and to develop more effective therapeutic strategies.

With the development of artificial intelligence, the application of machine learning to develop predictive models for sepsis-associated acute kidney injury has made potential breakthroughs in early identification, grading, diagnosis, and prognosis determination.

Here, we conducted a systematic search of the PubMed, Cochrane Library, Embase (Ovid), Web of Science, and Scopus databases on April 28, 2023, and screened relevant literature. Then, we comprehensively extracted relevant data related to machine learning algorithms, predictors, and predicted objectives. We subsequently performed a critical evaluation of research quality, data aggregation, and analyses.

We screened 25 studies on predictive models for sepsis-associated acute kidney injury from a total of originally identified 2898 studies. The most commonly used machine learning algorithm is traditional logistic regression, followed by eXtreme gradient boosting. We categorized these predictive models into early identification models (60%), prognostic prediction models (32%), and subtype identification models (8%) according to their predictive purpose. The five most commonly used predictors were serum creatinine levels, lactate levels, age, blood urea nitrogen concentration, and diabetes mellitus. In addition, a single data source, insufficient assessment of clinical utility, lack of model bias assessment, and hyperparameter adjustment may be the main reasons for the low quality of the current research.

However, studies on the nondeath prognostic outcomes, the long-term clinical outcomes, and the subtype identification models are insufficient. Additionally, the poor quality of the research and the insufficient practicality of the model are problems that need to be addressed urgently.