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.

Sepsis-associated hypotension or shock is a critical stage of sepsis, and a current clinical emergency that has high mortality and multiple complications. A new restrictive fluid resuscitation therapy has been applied, and its influence on patients' renal function remains unclear. The purpose of this study is to evaluate the influence of restrictive fluid resuscitation on incidence of severe acute kidney injury (AKI) in adult patients with sepsis hypotension and shock compared with usual care.

Systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

PubMed, Embase, Web of Science and Cochrane Library were searched through 1 November 2024.

We included randomised controlled trials that compared restrictive fluid resuscitation with liberal fluid therapy on patients with sepsis-associated hypotension and shock, to find out their effect on the incidence of severe AKI. Severe AKI was defined as the AKI network score 2-3 or Kidney Disease Improving Global Outcomes stages 2 and 3.

Two independent reviewers used standardised methods to search, screen and code included trials. Risk of bias was assessed using the Cochrane Systematic Review Handbook for randomised clinical trials. Meta-analysis was conducted using random effects models. Sensitivity and subgroup analyses, trial sequential analysis (TSA), Egger's test and the trim-and-fill method were performed. Findings were summarised in GRADE evidence profiles and synthesised qualitatively.

Nine trials (3718 participants) were included in this research and the analysis was conducted in random effects model. There was a significant difference in the incidence of severe AKI (risk ratio 0.87, 95% CI 0.79 to 0.96, p=0.006; I2=0%) and the duration of mechanical ventilation (mean difference -41.14, 95% CI -68.80 to -13.48; p=0.004; I2=74%) between patients receiving restrictive fluid resuscitation and patients receiving liberal fluid resuscitation. TSA showed that the cumulative amount of participants met the required information size, the positive conclusion had been confirmed. The GRADE assessment results demonstrated moderate confidence in the incidence of severe AKI, as well as the results of all second outcomes except the Intensive Care Unit length of stay (ICU LOS), which received limited confidence. The result of incidence of worse AKI was rated as of high certainty.

It is conclusive that fluid restriction strategy is superior to usual care when it comes to reducing the incidence of severe AKI in sepsis-associated hypotension and shock. Shorter duration of ventilation is concerned with fluid restriction as well, but the heterogeneity is substantial. GRADE assessments confirmed moderate and above certainty. Traditional fluid resuscitation therapy has the potential to be further explored for improvements to be more precise and appropriate for a better prognosis.

CRD42023449239.

The present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR‑21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑10, and gene expression of microRNA‑21 (miR‑21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR‑21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR‑21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low‑dose BA and BX in ameliorating sepsis‑induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.

Sepsis-induced renal damage poses a significant threat, necessitating effective therapeutic strategies. Cannabidiol (CBD) has beneficial effects on tissues and their functions by exhibiting antioxidant and anti-inflammatory effects. This study investigates the potential protective effects of CBD in mitigating lipopolysaccharide (LPS)-induced renal injury in Wistar Albino rats. Thirty-two Wistar Albino rats were categorized into control, LPS (5 mg/kg i.p.), LPS + CBD, and CBD (5 mg/kg i.p.) groups. After the experiment, samples were collected for biochemical, genetic, histopathological, and immunohistochemical analyses. Oxidative stress markers as total oxidant status (TOS) and total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), immune staining as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), caspase-3, gene expressions as nuclear factor erythroid 2-related factor 2 (NRF2), C/EBP homologous protein (CHOP), caspase-9, glucose-regulating protein 78 (GRP78), B-cell leukemia/lymphoma 2 (Bcl2), and tissue histology have been examined. The LPS-exposed group exhibited significant renal abnormalities, mitigated by CBD intervention in the LPS + CBD group. CBD reduced immunoexpression scores for TNF-α, caspase-3, and IL-10. Biochemically, CBD induced a positive shift in the oxidative balance, increasing TAS, SOD, and GPx, while decreasing TOS, OSI, and MDA levels. Genetic analyses highlighted CBD's regulatory impact on NRF2, CHOP, caspase-9, GRP78, and Bcl2, providing molecular insights into its protective role against LPS-induced renal damage. This study underscores CBD as a promising protective agent against sepsis-induced renal damage. Our findings could provide valuable insights into potential therapeutic avenues for addressing renal complications in sepsis.

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.

Microcirculatory dysfunction, hypoxia, and inflammation are considered to be central in the pathogenesis of sepsis-induced acute kidney injury (AKI). In this experimental study, we hypothesized that extracorporeal removal of inflammatory cytokines by hemoadsorption (HA) therapy may mitigate renal injury associated with sepsis-induced AKI. To this end, we investigated renal microcirculatory oxygenation and perfusion, oxygen consumption, lactate, systemic hemodynamic variables, tubular cell integrity, inflammatory mediators, and kidney function in a rat model of septic AKI elicited by endotoxin infusion. Three groups of rats were investigated on extracorporeal circulation: HA only, LPS, and LPS + HA. Endotoxin infusion reduced cortex microcirculatory oxygenation and raised creatinine and lactate levels. Renal microcirculatory oxygenation, measured by two independent techniques (phosphorescence (µPO2) and spectrophotometry/Doppler (µHbO2sat and [Formula: see text])), was ameliorated by HA therapy. The renal oxygen consumption, lactate and creatinine levels were restored in the LPS + HA group. A reduced amount of injured tubular cells was found in histological analysis of the kidneys. This experimental study demonstrated an improvement in multiple determinants of kidney oxygenation, damage, and systemic blood perfusion by HA in a clinically relevant rat model of septic AKI. Further studies are needed to optimize and support the clinical use of HA as a renal protective strategy.

Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis. miR-340-5p has been identified as an effective biomarker of various human diseases. As the downstream target, the involvement of lysine (K)-specific demethylase 4C (KDM4C) in SA-AKI would help interpret the regulatory mechanism of miR-340-5p. The significance of miR-340-5p in the onset and progression of SA-AKI was evaluated to provide a potential therapeutic target for SA-AKI.

This study enrolled 64 healthy individuals (control) and 159 sepsis patients (92 SA-AKI and 67 non-AKI) and collected urine samples. The urine level of miR-340-5p was analyzed by PCR, and a series of statistical analyses were conducted to assess the clinical significance of miR-340-5p in the occurrence and development of SA-AKI. The injured renal tubular epithelial cells were established with LPS induction. The roles of miR-340-5p in cellular processes were evaluated.

Increasing urine miR-340-5p discriminated SA-AKI patients from healthy individuals (AUC = 0.934) and non-AKI sepsis patients (AUC = 0.806) sensitively. Additionally, elevated miR-340-5p could predict the adverse prognosis (HR = 5.128, 95% CI = 1.259-20.892) and malignant development of SA-AKI patients. In vitro, lipopolysaccharide (LPS) also induced an increased level of miR-340-5p and significant cell injury in the renal tubular epithelial cell; silencing miR-340-5p could alleviate the suppressed proliferation, migration, and invasion caused by LPS. In mechanism, miR-340-5p negatively regulated KDM4C, which mediated the function of miR-340-5p.

miR-340-5p served as a diagnostic and prognostic biomarker of SA-AKI and regulated renal tubular epithelial cell injury via modulating KDM4C.

Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1-7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1-7) (1.0-25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 μM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B1 receptor (B1R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 μM (a B1R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1-7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1-7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1R, and kinin B2 receptor (B2R) showed no direct interaction between Ang-(1-7) with B1R or B2R. In conclusion, our findings suggest that Ang-(1-7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR.

Background: Sepsis-induced acute kidney injury (SI-AKI) is a kind of kidney dysfunction, which brings a lot of suffering. This study aimed to figure out the role of the miR-218-5p/PGC-1α axis in SI-AKI. Methods: AKI mouse model was established through cecal ligation and puncture. PGC-1α expression was activated using an activator ZLN005 before the serum and tissue samples were collected. Next, pathological structure and apoptosis of kidney tissues were observed. Levels of blood urea nitrogen, serum creatinine, and indicators of inflammation and oxidative stress were assessed. Moreover, reactive oxygen species and mitochondrial membrane potential levels, adenosine 5'-triphosphate content, and mitochondrial ultrastructure of kidney tissues were observed. HK2 cells were treated by lipopolysaccharide (LPS) to mimic sepsis in vitro , followed by evaluation of cell survival and apoptosis, inflammation, and oxidative stress. Subsequently, the binding relation between PGC-1α and miR-218-5p was predicted and validated. Then expression of PGC-1α and miR-218-5p was detected. PGC-1α and miR-218-5p expression were intervened to detect their influences in mitochondrial biogenesis. At last, miR-218-5p was overexpressed in ZLN005 (PGC-1α activating agent) pretreated SI-AKI mice to validate the mechanism. Results: PGC-1α is poorly expressed in SI-AKI, but overexpression of PGC-1α using ZLN005 alleviated SI-AKI injury and promoted mitochondrial biogenesis in AKI mice, and relieved LPS-induced cell injury. PGC-1α is a target of miR-218-5p. Downregulation of miR-218-5p expression in HK2 cells attenuated mitochondrial biogenesis disorder. Inhibition of PGC-1α annulled the role of miR-218-5p silencing in cells. In vivo , miR-218-5p overexpression partly reversed the protective role of ZLN005 in SI-AKI mice. Conclusion: miR-218-5p targeted PGC-1α to disrupt mitochondrial biogenesis, thereby exacerbating SI-AKI.

This study aimed to explore the underlying mechanisms of sepsis and acute kidney injury (AKI), including sepsis-associated AKI (SA-AKI), a frequent complication in critically ill sepsis patients.

GWAS data was analyzed for genetic association between AKI and sepsis. Then, we systematically applied three distinct machine learning algorithms (LASSO, SVM-RFE, RF) to rigorously identify and validate signature genes of SA-AKI, assessing their diagnostic and prognostic value through ROC curves and survival analysis. The study also examined the functional and immunological aspects of these genes, potential drug targets, and ceRNA networks. A mouse model of sepsis was created to test the reliability of these signature genes.

LDSC confirmed a positive genetic correlation between AKI and sepsis, although no significant shared loci were found. Bidirectional MR analysis indicated mutual increased risks of AKI and sepsis. Then, 311 key genes common to sepsis and AKI were identified, with 42 significantly linked to sepsis prognosis. Six genes, selected through LASSO, SVM-RFE, and RF algorithms, showed excellent predictive performance for sepsis, AKI, and SA-AKI. The models demonstrated near-perfect AUCs in both training and testing datasets, and a perfect AUC in a sepsis mouse model. Significant differences in immune cells, immune-related pathways, HLA, and checkpoint genes were found between high- and low-risk groups. The study identified 62 potential drug treatments for sepsis and AKI and constructed a ceRNA network.

The identified signature genes hold potential clinical applications, including prognostic evaluation and targeted therapeutic strategies for sepsis and AKI. However, further research is needed to confirm these findings.

Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis.

We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP.

A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP (< 63 mmHg) and high MPP (≥ 63 mmHg) groups using the optimal ROC curve-derived cut-off point. The incidence of AKI in the low MPP group was higher than that in the high MPP group (87.6% vs. 78.3%, P < 0.001). Multivariable logistic regression analysis adjusted for confounding factors revealed that each 1 mmHg increase in MPP as a continuous variable was associated with a 2% decrease in AKI incidence within 7 days of ICU admission (OR:0.98, 95%CI:0.97-0.99, P < 0.001). When MPP was used as a categorical variable, patients in the high MPP group had a lower risk of AKI than those in the low MPP group (OR:0.71, 95%CI:0.61-0.83, P = 0.001). Subgroup analyses demonstrated a consistent association between MPP and AKI risk across all variables assessed (P for interaction all > 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P < 0.0001).

Lower levels of MPP are associated with an increased incidence of AKI at 7 days in critically ill patients with sepsis.

To highlight progress and opportunities of measuring kidney size with MRI, and to inspire research into resolving the remaining methodological gaps and unanswered questions relating to kidney size assessment.

This work is not a comprehensive review of the literature but highlights valuable recent developments of MRI of kidney size.

The links between renal (patho)physiology and kidney size are outlined. Common methodological approaches for MRI of kidney size are reviewed. Techniques tailored for renal segmentation and quantification of kidney size are discussed. Frontier applications of kidney size monitoring in preclinical models and human studies are reviewed. Future directions of MRI of kidney size are explored.

MRI of kidney size matters. It will facilitate a growing range of (pre)clinical applications, and provide a springboard for new insights into renal (patho)physiology. As kidney size can be easily obtained from already established renal MRI protocols without the need for additional scans, this measurement should always accompany diagnostic MRI exams. Reconciling global kidney size changes with alterations in the size of specific renal layers is an important topic for further research. Acute kidney size measurements alone cannot distinguish between changes induced by alterations in the blood or the tubular volume fractions-this distinction requires further research into cartography of the renal blood and the tubular volumes.

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

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.

A woman in her 80s was admitted to the emergency department with an acute infective exacerbation of chronic obstructive pulmonary disease and type 2 respiratory failure, culminating in cardiac arrest for 2 min. She was successfully resuscitated, connected to a mechanical ventilator and subsequently transferred to the intensive care unit. Later in her hospital stay, the patient underwent a tracheostomy following prolonged intubation.During this period, she developed septic shock with complications, including acute kidney injury, metabolic acidosis and volume overload. As a result, the nephrologist recommended emergency haemodialysis. Initially, a left femoral haemodialysis catheter was established but had to be withdrawn a few days later due to the development of deep vein thrombosis (DVT). A left internal jugular catheter was then inserted but was removed after 5 days due to another DVT. It was subsequently replaced with a central line for vasopressor support.A Doppler scan revealed a large thrombus in the right internal jugular vein, extending to the area just above the superior vena cava. A similar thrombus was detected in the left internal jugular vein, with weak blood flow observed in both the right and left subclavian veins. Although the subclavian vein flows were deemed adequate, there was unsatisfactory blood flow through the catheter after insertion, rendering it unsuitable for haemodialysis.Due to an earlier central line-related infection, the right femoral site exhibited signs of infection and the presence of a pus pocket, making it unsuitable for haemodialysis access. To address this, the right popliteal vein was chosen for catheterisation using a 20-cm, 12 French catheter, the longest available catheter in the country at the time. The patient was placed in a prone position, and the catheter was smoothly inserted with ultrasound guidance, resulting in good flow. Subsequent haemodialysis sessions were carried out regularly.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid deterioration in renal function, manifested by a significant increase in creatinine and a sharp decrease in urine output. The incidence of morbidity and mortality associated with AKI is on the rise, with most patients progressing to chronic kidney disease or end-stage renal disease. Treatment options for patients with AKI remain limited. Circular RNA (circRNA) is a wide and diverse class of non-coding RNAs that are present in a variety of organisms and are involved in gene expression regulation. Studies have shown that circRNA acts as a competing RNA, is involved in disease occurrence and development, and has potential as a disease diagnostic and prognostic marker. CircRNA is involved in the regulation of important biological processes, including apoptosis, oxidative stress, and inflammation. This study reviews the current status and progress of circRNA research in the context of AKI.

Sivelestat, a selective inhibitor of neutrophil elastase (NE), can mitigate sepsis-related acute lung injury. However, the role of sivelestat in inhibiting oxidative stress and attenuating sepsis-related acute kidney injury (AKI) remains unclear. Here, we reported the effects of sivelestat against oxidative stress-induced AKI by suppressing the production of oxidative stress indicators.

A male Sprague-Dawley rat model of sepsis was established by cecal ligation and puncture (CLP). Sivelestat or normal saline was administered into jugular vein with a sustained-release drug delivery system. Indicators of inflammation and AKI, including white blood cells (WBC), neutrophils, lymphocytes, C-reactive proteins (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA), were assessed at 24 h post-sivelestat treatment. Indicators of liver injury, including direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were also assessed at 24 h post-sivelestat treatment. Indicators of oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), were assessed at 12 h and 24 h post-sivelestat treatment. At 24 h post-sivelestat treatment, H&E staining of kidney and liver tissue was performed to observe pathological alterations.

At 24 h post normal saline or sivelestat (0.2 g/kg body weight) treatment, WBC, neutrophil, CRP, PCT, MDA, BUN, Cr, UA, AST, ALT, DBIL and IBIL were increased, while SOD and GSH-Px were decreased, in septic rats treated with normal saline compared with that in non-septic rats treated with normal saline (all p < 0.05). The changes of these indicators were reversed in septic rats treated with sivelestat compared with that in septic rats treated with normal saline (all p < 0.05). Similar results were found regarding the levels of oxidative stress indicators at 12 h post-sivelestat treatment. The degenerative histopathological changes in both kidney and liver tissues were ameliorated upon sivelestat treatment.

Sivelestat plays a protective role in sepsis-related AKI by inhibiting oxidative stress. Our study reveals a possible therapeutic potential of sivelestat for oxidative stress-induced AKI.

Renal pathologies often manifest as alterations in kidney size, providing a valuable avenue for employing dynamic parametric MRI as a means to derive kidney size measurements for the diagnosis, treatment, and monitoring of renal disease. Furthermore, this approach holds significant potential in supporting MRI data-driven preclinical investigations into the intricate mechanisms underlying renal pathophysiology. The integration of deep learning algorithms is crucial in achieving rapid and precise segmentation of the kidney from temporally resolved parametric MRI, facilitating the use of kidney size as a meaningful (pre)clinical biomarker for renal disease. To explore this potential, we employed dynamic parametric T2 mapping of the kidney in rats in conjunction with a custom-tailored deep dilated U-Net (DDU-Net) architecture. The architecture was trained, validated, and tested on manually segmented ground truth kidney data, with benchmarking against an analytical segmentation model and a self-configuring no new U-Net. Subsequently, we applied our approach to in vivo longitudinal MRI data, incorporating interventions that emulate clinically relevant scenarios in rats. Our approach achieved high performance metrics, including a Dice coefficient of 0.98, coefficient of determination of 0.92, and a mean absolute percentage error of 1.1% compared with ground truth. The DDU-Net enabled automated and accurate quantification of acute changes in kidney size, such as aortic occlusion (-8% ± 1%), venous occlusion (5% ± 1%), furosemide administration (2% ± 1%), hypoxemia (-2% ± 1%), and contrast agent-induced acute kidney injury (11% ± 1%). This approach can potentially be instrumental for the development of dynamic parametric MRI-based tools for kidney disorders, offering unparalleled insights into renal pathophysiology.

To assess the association between the systemic inflammation response index (SIRI) and the prognosis in patients with sepsis-associated acute kidney injury (SA-AKI).

In this observational study, adult patients with SA-AKI were categorized into three groups based on SIRI tertiles. Survival outcomes were compared across the three groups using Kaplan-Meier survival curves. Various Cox proportional hazards regression models were developed to determine the association between the SIRI and mortality in patients with SA-AKI. Subgroup analyses were also performed to explore the association between different SIRI tertiles and all-cause mortality.

After adjusting for several confounders, the second SIRI tertile (2.5 < SIRI < 7.6) was found to be an independent risk factor for 30-day mortality [hazard ratio (95% confidence interval): 1.19 (1.01-1.40)], 90-day mortality [1.22 (1.06-1.41)], and 365-day mortality [1.24 (1.09-1.40)]. Furthermore, high SIRI values were associated with increased risks of 30-day, 90-day, and 365-day mortality in patients with SA-AKI across all three models. The third tertile showed a significant association with adverse outcomes in most subgroups.

The SIRI serves as a comprehensive biomarker for predicting all-cause mortality of critically ill patients with SA-AKI.

Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI.

Acute kidney injury (AKI) is a global health threat due to its high morbidity and mortality. There is still a lack of effective therapeutic methods to deal with AKI clinically. Natural products with outstanding accessibility and bioactivity are potential candidates for AKI treatment. Natural product-based prodrugs or nano-structures with improved properties are frequently fabricated for maximizing bioavailability and decreasing side effects, in which natural polymers are selected as carriers, or natural drugs are loaded as cargos on designed polymers. In this review, the etiologies of AKI are briefly presented, and emerging natural products delivered rationally for AKI therapy, as either carriers or cargos, are both introduced. Moreover, the challenges of the future development of nature-based nanodrugs or prodrugs for AKI have also been discussed.

Acute kidney injury (AKI) is one of the most severe complications of sepsis. This study was conducted to analyze the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecular-1 (uKIM-1), and urinary angiotensinogen (uAGT) in the early diagnosis and mortality prediction of septic AKI.

The prospective study enrolled 80 sepsis patients in the ICU and 100 healthy individuals and divided patients into an AKI group and a non-AKI group. uNGAL, uKIM-1, uAGT, serum creatinine/procalcitonin/C-reaction protein, and other indicators were determined, and clinical prediction scores were recorded. The sensitivity and specificity of uNGAL, uKIM-1, and uAGT in diagnosis and mortality prediction were analyzed by the receiver operator characteristic (ROC) curve and the area under the curve (AUC).

uNGAL, uKIM-1, and uAGT levels were higher in sepsis patients than healthy controls, higher in AKI patients than non-AKI patients, and higher in AKI-2 and AKI-3 patients than AKI-1 patients. At 0 h after admission, the combined efficacy of three indicators in septic AKI diagnosis (ROC-AUC: 0.770; sensitivity: 82.5%; specificity: 70.0%) was better than a single indicator. At 24 h, uNGAL, uKIM-1, and uAGT levels were higher in sepsis non-survivals than survivals and higher in septic AKI non-survivals than septic AKI survivals. The combined efficacy of three indicators in the prediction of sepsis/septic AKI mortality (ROC-AUC: 0.828/0.847; sensitivity: 71.4%/100.0%; specificity: 82.7%/66.7%) was better than a single indicator.

uNGAL, uKIM-1, and uAGT levels were increased in septic AKI, and their combination helped the early diagnosis and mortality prediction.

Acute kidney injury (AKI) is one of the common complications in patients with sepsis. We aimed to investigate the protective mechanism of salidroside (SLDS) on AKI induced by cecal ligation and perforation (CLP). We established a sepsis model using the CLP, and pretreated the mice with SLDS. We used biochemical methods to measure renal function, inflammatory factors and oxidase levels. We used transmission electron microscopy to observe mitochondrial damage, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) to detect apoptosis in renal tubular epithelial cells (TECs), and RT-quantitative PCR (qPCR) to detect the expression of apoptotic genes. CLP induced renal pathological damage and decreased renal function, activated inflammatory factors and oxidases, leading to mitochondrial damage and increased apoptosis of TECs. SLDS pretreatment improved renal pathological damage, reduced tumor necrosis factor (TNF)-α, interleukin (IL)-6 and malondialdehyde levels, and increased the levels of glutathione peroxidase, superoxide dismutase and catalase. Moreover, SLDS stabilized mitochondrial damage induced by CLP, inhibited TECs apoptosis, increased Bcl-2 mRNA level, and decreased Bax and Caspase-3 mRNA levels. SLDS protects CLP induced AKI by inhibiting oxidative stress, mitochondrial damage, and cell apoptosis in TECs.

Renal diseases pose a significant socio-economic burden on healthcare systems. The development of better diagnostics and prognostics is well-recognized as a key strategy to resolve these challenges. Central to these developments are MRI biomarkers, due to their potential for monitoring of early pathophysiological changes, renal disease progression or treatment effects. The surge in renal MRI involves major cross-domain initiatives, large clinical studies, and educational programs. In parallel with these translational efforts, the need for greater (patho)physiological specificity remains, to enable engagement with clinical nephrologists and increase the associated health impact. The ISMRM 2022 Member Initiated Symposium (MIS) on renal MRI spotlighted this issue with the goal of inspiring more solutions from the ISMRM community. This work is a summary of the MIS presentations devoted to: 1) educating imaging scientists and clinicians on renal (patho)physiology and demands from clinical nephrologists, 2) elucidating the connection of MRI parameters with renal physiology, 3) presenting the current state of leading MR surrogates in assessing renal structure and functions as well as their next generation of innovation, and 4) describing the potential of these imaging markers for providing clinically meaningful renal characterization to guide or supplement clinical decision making. We hope to continue momentum of recent years and introduce new entrants to the development process, connecting (patho)physiology with (bio)physics, and conceiving new clinical applications. We envision this process to benefit from cross-disciplinary collaboration and analogous efforts in other body organs, but also to maximally leverage the unique opportunities of renal physiology. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Circular RNAs (circRNAs) has been manifested to be involved in the development of human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, the function and mechanism of circ_0006944 in SA-AKI has not been validated. Lipopolysaccharide (LPS) was utilised to induce AKI cell model. Levels of genes and proteins were monitored by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell counting kit 8 assay, EdU assay and flow cytometry were exploited to estimate cell proliferation and apoptosis. The concentrations of inflammation factors were measured via using ELISA assay. The levels of MDA and SOD were tested by the corresponding kits. The relationship between miR-205-5p and circ_0006944 or UBL4A was verified by dual-luciferase reporter assay and RIP assay. Circ_0006944 was overexpressed in SA-AKI patients, and interference of circ_0006944 restrained LPS-stimulated HK2 cell proliferation repression, apoptosis, inflammation and oxidative stress. Mechanistically, circ_0006944 could sponge miR-205-5p, and miR-205-5p interference counteracted circ_0006944 inhibition-mediated impact on the biological functions in LPS-induced HK2 cell. Additionally, UBL4A was targeted by miR-205-5p, and UBL4A overexpression also partially abolished the repressive impacts of miR-205-5p on LPS-triggered HK2 cell damage. Importantly, circ_0006944 sponged miR-205-5p to mediate the expression of UBL4A. Our outcomes identified that circ_0006944 exacerbated SA-AKI development via miR-205-5p/UBL4A axis, which might be a potential treatment and diagnosis biomarker for SA-AKI.

Acute kidney injury (AKI) is a complex syndrome which affects a significant proportion of hospitalized children. The breadth and impact of AKI on health outcomes in both adults and children have come to the fore in recent years with increasing awareness encouraging research advancement. Despite this, management strategies for most types of AKI remain heavily reliant on fluid and electrolyte management, hemodynamic optimization, nephrotoxin avoidance and appropriate initiation of kidney replacement therapy. Specific drugs targeting the mechanisms involved in AKI remain elusive. Recent improvement in appreciation of the complexity of AKI pathophysiology has allowed for greater opportunity to consider novel therapeutic agents. A number of drugs specifically targeting AKI are in various stages of development. This review will consider some novel and repurposed agents; interrogate the plausibility of the proposed mechanisms of action, as they relate to what we know about the pathophysiology of AKI; and review the level of existing literature supporting their efficacy. The evidence base, particularly in children, is limited.

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

The efficacy of dexmedetomidine was elusive for septic shock. This meta-analysis aimed to explore the efficacy of dexmedetomidine for septic shock.

PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched through October 2022 and we included randomized controlled trials reporting the effect of dexmedetomidine in patients with septic shock.

Five randomized controlled trials were included in the meta-analysis. Compared with control group for septic shock, dexmedetomidine treatment was able to substantially decrease Sequential Organ Failure Assessment score (mean difference [MD] = -0.99; 95% confidence interval [CI] = -1.14 to -0.84; P < .00001) and duration of mechanical ventilation (MD = -0.90; 95% CI = -1.27 to -0.54; P < .00001), but showed no obvious influence on morality at 28 days (odds ratio = 0.79; 95% CI = 0.38 to 1.66; P = 054), hospital mortality (odds ratio = 0.66; 95% CI = 0.35 to 1.24; P = .20) or intensive care unit length of stay (MD = -1.47; 95% CI = -4.60 to 1.66; P = .36).

Dexmedetomidine administration may help treat patients with septic shock.

Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.

Sepsis is a grave medical disorder characterized by a systemic inflammatory response to infection. Furthermore, it is a leading cause of morbidity and mortality, especially in hospitalized patients. Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality. Patients with burns are particularly vulnerable to developing sepsis and AKI due to the extensive tissue damage and immune suppression resulting from burn injury. In this study, unsupervised clustering algorithms were used to track longitudinal biomarkers in patients with burns and assess their impact on mortality.

This retrospective study included adult patients with burns aged ≥ 18 years, who were admitted to the burn intensive care unit of Hallym University and Hangang Sacred Heart Hospital between July 2010 and December 2021. The patients were divided into two subgroups: those with sepsis (538 patients) and those without sepsis (826 patients). The longitudinal biomarkers were grouped into three clusters using the k-means clustering algorithm. Each cluster was assigned a letter from A to C according to its mortality rate.

The odds ratio (OR) of pH was 9.992 in the positive group and 31.745 in the negative group in cluster C. The OR for lactate dehydrogenase (LD) was 3.704 in the positive group and 6.631 in the negative group in cluster C. The OR for creatinine was 2.784 in the positive group and 8.796 in the negative group in cluster C. The OR for blood urea nitrogen (BUN) in the negative group was 0.348, indicating a negative predictor of mortality. Regarding the application of Continuous Renal Replacement Therapy (CRRT) and ventilation, ventilation was significant in both groups. In contrast, CRRT application was not significant in the sepsis-positive group. Furthermore, it was not selected as a variable in the negative group.

The pH, LD, and creatinine were significant in both groups, while lactate and platelets were significant in the sepsis-positive group. In addition, albumin, glucose, and BUN were significant in the sepsis-negative group. Continuous renal replacement therapy was not significant in either group. However, the use of a ventilator was associated with poor prognosis.

Pyogenic vertebral osteomyelitis represents a clinical challenge associated with significant morbidity and mortality. The aim of this study was to analyze potential risk factors for the in-hospital mortality of vertebral osteomyelitis (VO) patients.

Based on the International Classification of Diseases, 10th Revision (ICD-10) codes for VO ("M46.2-", "M46.3-", and "M46.4-") data for total case numbers, secondary diagnoses, and numbers of in-hospital deaths were extracted from the Institute for the Hospital Remuneration System (InEK GmbH). Odds ratios (OR) for death were calculated for several secondary diseases and factors of interest.

Despite age, certain comorbidities were found to be strongly associated with increased mortality risk: Heart failure (OR = 2.80; 95% CI 2.45 to 3.20; p < 0.01), chronic kidney disease (OR = 1.83; 95% CI 1.57 to 2.13; p < 0.01), and diabetes with complications (OR = 1.86; 95% CI 1.46 to 2.38; p < 0.01). Among the complications, acute liver failure showed the highest risk for in-hospital mortality (OR = 42.41; 95% CI 23.47 to 76.62; p < 0.01). Additionally, stage III kidney failure (OR = 9.81; 95% CI 7.96 to 12.08; p < 0.01), sepsis (OR = 5.94; 95% CI 5.02 to 7.03; p < 0.01), acute respiratory failure (OR = 5.31; 95% CI 4.61 to 6.12; p < 0.01), and systemic inflammatory response syndrome (SIRS) (OR = 5.19; 95% CI 3.69 to 5.19; p < 0.01) were associated with in-hospital mortality. When analyzing the influence of pathogens, documented infection with Pseudomonas aeruginosa had the highest risk for mortality (OR = 2.74; 95% CI 2.07 to 3.63; p < 0.01), followed by Streptococci, Escherichia coli, and Staphylococcus aureus infections.

An early assessment of individual patient risk factors may be beneficial in the care and treatment of VO to help reduce the risks of mortality. These findings emphasize the importance of closely monitoring VO patients with chronic organ diseases, early detection and treatment of sepsis, and tailored empirical antibiotic therapy. The identification of specific pathogens and antibiotic susceptibility testing should be prioritized to improve patient outcomes in this high-risk population.

Cepabiflas B and C (CBs) are flavonoid dimers separated from Allium cepa. They demonstrated antioxidant and α-glucosidase and protein tyrosine phosphatase 1B inhibition capacities. However, their anti-inflammatory activities and their effects on endotoxemia are unknown. The current study aimed at exploring the protective activities of CBs on lipopolysaccharide (LPS)-induced kidney and liver damage in mice and investigating the possible molecular mechanisms. Mice were orally treated with a low (40 mg/kg) or high (60 mg/kg) dose of CBs for five days prior to a single intraperitoneal injection of LPS (10 mg/kg). Samples of serum and hepatic and kidney tissues were collected 24 h after the LPS challenge. Changes in serum indices of hepatic and renal injury, pathological changes, molecular biological parameters, and proteins/genes related to inflammation and apoptosis of these organs were estimated. LPS injection resulted in deleterious injury to both organs as indicated by elevation of serum ALT, AST, creatinine, and BUN. The deteriorated histopathology of hepatic and renal tissues confirmed the biochemical indices. CBs treated groups showed a reduction in these parameters and improved histopathological injurious effects of LPS. LPS-induced hepatorenal injury was linked to elevated oxidative stress as indicated by high levels of MDA, 4-HNE, as well as repressed antioxidants (TAC, SOD, and GSH) in hepatic and kidney tissues. This was accompanied with suppressed Nrf2/HO-1 activity. Additionally, there was a remarkable inflammatory response in both organs as NF-κB signalling was activated and high levels of downstream cytokines were produced following the LPS challenge. Apoptotic changes were observed as the level and gene expression of Bax and caspase-3 were elevated along with declined level and gene expression of Bcl2. Interestingly, CBs reversed all these molecular and genetic changes and restricted oxidative inflammatory and apoptotic parameters after LPS-injection. Collectedly, our findings suggested the marked anti-inflammatory and anti-apoptotic activity of CBs which encouraged its use as a new candidate for septic patients.

Sepsis-associated acute kidney injury (SA-AKI) results in significant morbidity and mortality, and ferroptosis may play a role in its pathogenesis. Our aim was to examine the effect of exogenous H₂S (GYY4137) on ferroptosis and AKI in in vivo and in vitro models of sepsis and explore the possible mechanism involved. Sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice, which were randomly divided into the sham, CLP, and CLP + GYY4137 group. The indicators of SA-AKI were most prominent at 24 h after CLP, and analysis of the protein expression of ferroptosis indicators showed that ferroptosis was also exacerbated at 24 h after CLP. Moreover, the level of the endogenous H₂S synthase CSE (Cystathionine-γ-lyase) and endogenous H₂S significantly decreased after CLP. Treatment with GYY4137 reversed or attenuated all these changes. In the in vitro experiments, LPS was used to simulate SA-AKI in mouse renal glomerular endothelial cells (MRGECs). Measurement of ferroptosis-related markers and products of mitochondrial oxidative stress showed that GYY4137 could attenuate ferroptosis and regulate mitochondrial oxidative stress. These findings imply that GYY4137 alleviates SA-AKI by inhibiting ferroptosis triggered by excessive mitochondrial oxidative stress. Thus, GYY4137 may be an effective drug for the clinical treatment of SA-AKI.

Sepsis-related AKI is related to short-term mortality and poor long-term prognoses, such as chronic renal insufficiency, late development of end-stage renal disease, and long-term mortality. In this study, we aimed to investigate the association of hyperuricemia with acute kidney injury (AKI) in patients with sepsis.

The retrospective cohort study included 634 adult sepsis patients hospitalized in the intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2020 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020. Based on the first serum uric acid level within 24 h of admission to the ICU, patients were divided into groups with or without hyperuricemia, and the incidence of AKI within seven days of ICU admission was compared between the two groups. The univariate analysis analyzed the effect of hyperuricemia on sepsis-related AKI, and the multivariable logistic regression model analysis was used.

Among the 634 patients with sepsis, 163 (25.7%) developed hyperuricemia, and 324 (51.5%) developed AKI. The incidence of AKI in the groups with and without hyperuricemia was 76.7% and 42.3%, respectively, with statistically significant differences (2 = 57.469, P < 0.001). After adjusting for genders, comorbidities (coronary artery disease), organ failure assessment (SOFA) score on the day of admission, basal renal function, serum lactate, calcitonin, and mean arterial pressure, hyperuricemia was showed to be an independent risk factor for AKI in patients with sepsis (OR = 4.415, 95%CI 2.793 ~ 6.980, P < 0.001). For every 1 mg/dL increase in serum uric acid in patients with sepsis, the risk of AKI increased by 31.7% ( OR = 1.317, 95%CI 1.223 ~ 1.418, P < 0.001).

AKI is a common complication in septic patients hospitalized in the ICU, and hyperuricemia is an independent risk factor for AKI in septic patients.

Despite all epidemiological, clinical, and experimental research efforts, therapeutic concepts in sepsis and sepsis-induced multi-organ dysfunction syndrome (MODS) remain limited and unsatisfactory. Currently, gene expression data sets are widely utilized to discover new biomarkers and therapeutic targets in diseases. In the present study, we analyzed MODS expression profiles (comprising 13 sepsis and 8 control samples) retrieved from NCBI-GEO and found 359 differentially expressed genes (DEGs), among which 170 were downregulated and 189 were upregulated. Next, we employed the weighted gene co-expression network analysis (WGCNA) to establish a MODS-associated gene co-expression network (weighted) and identified representative module genes having an elevated correlation with age. Based on the results, a turquoise module was picked as our hub module. Further, we constructed the PPI network comprising 35 hub module DEGs. The DEGs involved in the highest-confidence PPI network were utilized for collecting pathway and gene ontology (GO) terms using various libraries. Nucleotide di- and triphosphate biosynthesis and interconversion was the most significant pathway. Also, 3 DEGs within our PPI network were involved in the top 5 significantly enriched ontology terms, with hypercortisolism being the most significant term. PRKAR1A was the overlapping gene between top 5 significant pathways and GO terms, respectively. PRKAR1A was considered as a therapeutic target in MODS, and 2992 ligands were screened for binding with PRKAR1A. Among these ligands, 3 molecules based on CDOCKER score (molecular dynamics simulated-based score, which allows us to rank the binding poses according to their quality and to identify the best pose for each system) and crucial interaction with human PRKAR1A coding protein and protein kinase-cyclic nucleotide binding domains (PKA RI alpha CNB-B domain) via active site binding residues, viz. Val283, Val302, Gln304, Val315, Ile327, Ala336, Ala337, Val339, Tyr373, and Asn374, were considered as lead molecules.

The high mortality rate in sepsis patients is related to sepsis-associated liver injury (SALI). We sought to develop an accurate forecasting nomogram to estimate individual 90-day mortality in SALI patients. Data from 34,329 patients were extracted from the public Medical Information Mart for Intensive Care (MIMIC-IV) database. SALI was defined by total bilirubin (TBIL) > 2 mg/dL and the occurrence of an international normalized ratio (INR) > 1.5 in the presence of sepsis. Logistic regression analysis was performed to establish a prediction model called the nomogram based on the training set (n = 727), which was subsequently subjected to internal validation. Multivariate logistic regression analysis showed that SALI was an independent risk factor for mortality in patients with sepsis. The Kaplan‒Meier curves for 90-day survival were different between the SALI and non-SALI groups after propensity score matching (PSM) (log rank: P < 0.001 versus P = 0.038), regardless of PSM balance. The nomogram demonstrated better discrimination than the sequential organ failure assessment (SOFA) score, logistic organ dysfunction system (LODS) score, simplified acute physiology II (SAPS II) score, and Albumin-Bilirubin (ALBI) score in the training and validation sets, with areas under the receiver operating characteristic curve (AUROC) of 0.778 (95% CI 0.730-0.799, P < 0.001) and 0.804 (95% CI 0.713-0.820, P < 0.001), respectively. The calibration plot showed that the nomogram was sufficiently successful to predict the probability of 90-day mortality in both groups. The DCA of the nomogram demonstrated a higher net benefit regarding clinical usefulness than SOFA, LODS, SAPSII, and ALBI scores in the two groups. The nomogram performs exceptionally well in predicting the 90-day mortality rate in SALI patients, which can be used to assess the prognosis of patients with SALI and may assist in guiding clinical practice to enhance patient outcomes.

Although systolic blood pressure (SBP) is associated with acute renal injury (AKI), the relationship between baseline SBP and prognosis in critically ill patients with AKI is unclear. We aimed to assess the linearity and profile of the relationship between SBP at intensive care unit (ICU) admission and in-hospital mortality in these patients.

Data of AKI patients in the ICU settings were extracted from the Medical Information Mart for Intensive Care III database. The association between seven SBP categories (< 100, 100-109, 110-119, 120-129, 130-139, 140-149, and ≥ 150 mmHg) and all-cause in-hospital mortality was assessed by Cox proportional hazard models. Restricted cubic spline analysis for the multivariate Cox model was performed to explore the shape of the relationship between SBP and mortality.

A total of 24,202 patients with AKI were included in this study. A typically U-shaped relationship was found between SBP at admission and in-hospital mortality. Among all SBP categories, the lowest risk of death was observed in patients with SBP around 110-119 mmHg, whereas the highest was noted in patients with extremely low SBP (< 100 mmHg), followed by those with extremely high SBP (≥ 150 mmHg). SBP showed a significant interaction with vasopressor use and AKI stage in relation to the risk of in-hospital mortality.

SBP upon admission showed a non-linear association with all-cause in-hospital mortality in critically ill patients with AKI. Patients with low or high SBP show an increased risk of mortality compared to patients with normal SBP.

Sepsis, the most serious complication of infection, occurs when a cascade of potentially life-threatening inflammatory responses is triggered. Potentially life-threatening septic shock is a complication of sepsis that occurs when hemodynamic instability occurs. Septic shock may cause organ failure, most commonly involving the kidneys. The pathophysiology and hemodynamic mechanisms of acute kidney injury in the case of sepsis or septic shock remain to be elucidated, but previous studies have suggested multiple possible mechanisms or the interplay of multiple mechanisms. Norepinephrine is used as the first-line vasopressor in the management of septic shock. Studies have reported different hemodynamic effects of norepinephrine on renal circulation, with some suggesting that it could possibly exacerbate acute kidney injury caused by septic shock. This narrative review briefly covers the updates on sepsis and septic shock regarding definitions, statistics, diagnosis, and management, with an explanation of the putative pathophysiological mechanisms and hemodynamic changes, as well as updated evidence. Sepsis-associated acute kidney injury remains a major burden on the healthcare system. This review aims to improve the real-world clinical understanding of the possible adverse outcomes of norepinephrine use in sepsis-associated acute kidney injury.

Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T₂ and T₂ * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here, we used dynamic MRI to monitor KS for physiological interpretation of T₂ * and T₂ changes in acute pathophysiological scenarios.

KS was determined from T₂ *, T₂ mapping in rats. Six interventions that acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions that change the blood and/or tubular volume. A biophysical model was used to estimate changes in O₂ saturation of hemoglobin from changes in T₂ * and KS.

Upon aortic occlusion KS decreased; this correlated with a decrease in T₂ *, T₂ . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T₂ *, T₂ . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T₂ *, T₂ . Hypoxemia induced mild reductions in KS and T₂ *, T₂ . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T₂ *, T₂ followed by a decrease. Furosemide caused T₂ *, T₂ elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T₂ *.

Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T₂ *, T₂ . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies.

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (²³ Na-MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia-reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of ²³ Na-MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p = 0.0180, p = 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the ²³ Na medulla/cortex ratio, and plasma creatinine (R²  = 0.8009, p = 0.0117). The ²³ Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving ²³ Na-MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.