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Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p

Acute kidney injury (AKI) is increasing in prevalence and causes a global health burden. AKI is associated with significant mortality and can subsequently develop into chronic kidney disease (CKD). The kidney is one of the most energy-demanding organs in the human body and has a role in active solute transport, maintenance of electrochemical gradients, and regulation of fluid balance. Renal proximal tubular cells (PTCs) are the primary segment to reabsorb and secrete various solutes and take part in AKI initiation. Mitochondria, which are enriched in PTCs, are the main source of adenosine triphosphate (ATP) in cells as generated through oxidative phosphorylation. Mitochondrial dysfunction may result in reactive oxygen species (ROS) production, impaired biogenesis, oxidative stress multiplication, and ultimately leading to cell death. Even though mitochondrial damage and malfunction have been observed in both human kidney disease and animal models of AKI and CKD, the mechanism of mitochondrial signaling in PTC for AKI-to-CKD transition remains unknown. We review the recent findings of the development of AKI-to-CKD transition with a focus on mitochondrial disorders in PTCs. We propose that mitochondrial signaling is a key mechanism of the progression of AKI to CKD and potential targeting for treatment.

Background: Acute kidney injury (AKI) occurs frequently in ST-elevation myocardial infarction with cardiogenic shock (CS-STEMI) and is a strong independent prognostic marker for short and intermediate-term outcomes. Owing to the delayed presentation and limited facilities for primary percutaneous coronary intervention in low- and middle-income countries, the incidence, predictors, and outcome of AKI are likely to be different compared to the developed countries. We performed a post hoc analysis of patients presenting with CS-STEMI over 7 years (2016–2022) at a tertiary referral center in North India. The primary outcome assessed was AKI and the secondary outcome was in-hospital mortality. Results: Of the 426 patients, 194 (45.5%) patients developed AKI, as defined by the Kidney Disease Improving Global Outcomes criteria. Left ventricular (LV) pump failure with pulmonary edema [Odds ratio (OR) 1.67; 95% confidence interval (CI) 1.04–2.67], LV ejection fraction (OR 1.35 per 10% decrease in ejection fraction; CI 1.04–1.73), complete heart block (OR 2.06; CI 1.2–3.53), right ventricular infarction (OR 2.76; CI 1.39–5.49), mechanical complications (OR 3.89; CI 1.85–8.21), ventricular tachycardia (OR 2.80; CI 1.57–4.99), and non-revascularization (OR 2.2; CI 1.33–3.67) were independent predictors of AKI in multivariate logistic regression analysis. Additionally, AKI was a strong predictor of in-hospital mortality (univariate OR 30.61, CI 17.37–53.95). Conclusions: There is a higher incidence of AKI in CS-STEMI in resource-limited settings and is associated with adverse short-term outcomes. Additional studies are needed to address the optimal strategies for the prevention and management of AKI in such settings. [ABSTRACT FROM AUTHOR]

Sepsis associated Acute kidney injury (AKI) is a common clinical syndrome characterized by suddenly decreased in renal function and urinary volume. This study was designed to investigate the role of Aquaporin 1 (AQP1) and P53 in the development of sepsis-induced AKI and their potential regulatorymechanisms. Firstly, transcriptome sequencing analysis of mice kidney showed AQP1 expression was reduced and P53 expression was elevated in Cecal ligation and puncture (CLP)- induced AKI compared with controls. Bioinformatics confirmed that AQP1 expression was remarkably decreased and P53 expression was obviously elevated in renal tissues or peripheral blood of septic AKI patients. Moreover, we found in vivo experiments that AQP1mRNA levels were dramatically decreased and P53mRNA significantly increased following the increased expression of inflammation, apoptosis, fibrosis, NGAL and KIM-1 at various periods in septic AKI. Meanwhile, AQP1 and P53 protein levels increased significantly first and then decreased gradually in kidney tissue and serum of rats in different stages of septic AKI. Most importantly, in vivo and vitro experiments demonstrated that silencing of AQP1 greatly exacerbates renal or cellular injury by upregulating P53 expression promoting inflammatory response, apoptosis and fibrosis. Overexpression of AQP1 prevented the elevation of inflammation, apoptosis and fibrosis by down-regulating P53 expression in Lipopolysaccharide (LPS)-induced AKI or HK-2 cells. Therefore, our results suggested that AQP1 plays a protective role in modulating AKI and can attenuate inflammatory response, apoptosis and fibrosis via downregulating P53 in septic AKI or LPS-induced HK-2cells. The pharmacological targeting of AQP1mediated P53 expressionmight be identified as potential targets for the early treatment of septic AKI. [ABSTRACT FROM AUTHOR]

Background: There is accumulating evidence regarding the benefits of the 5-HT3 receptor antagonist ondansetron for the treatment of critical illness due to its potential anti-inflammatory effect. This study attempted to determine the potential targets and molecular mechanisms of ondansetron's action against critical illnesses. Methods: A bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets and the signaling pathways of ondansetron action against the most common critical illnesses such as acute kidney injury (AKI), sepsis, and acute respiratory distress syndrome (ARDS). Experiments of LPS- stimulated rat neutrophilswith ondansetron treatmentwere conducted to further validate the relevant hypothesis. Results: A total of 198, 111, and 26 primary causal targets were identified fromthe data for the action of ondansetron against AKI, sepsis, and ARDS respectively. We found that the pathway of neutrophil extracellular traps (NETs) formation is statistically significantly involved in the action of ondansetron against these three critical illnesses. In the pathway of NETs formation, the common drug- disease intersection targets in these three critical illnesses were toll-like receptor 8(TLR8),mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B1 (NFKB1), neutrophil elastase (NE), andmyeloperoxidase (MPO). Considering these bioinformatics findings, we concluded that ondansetron anti-critical illness effects are mechanistically and pharmacologically implicated with suppression of neutrophils-associated inflammatory processes. It was also showed that after treatment of LPS-stimulated rat neutrophils with ondansetron, the key proteins NE, MPO, and Peptide Arginine Deaminase 4 (PAD4) in the NETs formation were significantly reduced, and the inflammatory factors IL-6, IL-1β, TNF-α, and chemokine receptor (CXCR4) were also significantly decreased. Conclusion: The excessive formation of NETsmay have important research value in the development and progression of critical illness. Ondansetron may reduce excessive inflammatory injury in critical diseases by reducing the formation of NETs via influencing the five targets: TLR8, NFKB1, MAPK14, NE, and MPO. Ondansetron and these primary predictive biotargets may potentially be used to treat critical illness in future clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. Methods: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. Results: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. Conclusion: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) increases morbidity and mortality. Our study aimed to investigate the role of baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) as a predictor of AKI following TAVI. All consecutive TAVI patients were included in the analysis, except patients with dialysis and those with a GFR < 15 ml/min/1.73 m2 at baseline. Rates of AKI after TAVI were assessed according to the updated valve academic research consortium definitions using AKIN classification in three stages. NT-proBNP was measured at baseline. One-year mortality rates were assessed. We included 1973 patients treated with TAVI between January 2006 and December 2016. Median [IQR] age was 81.0 [77.0;84.0] years, the STS score was 6.2 [3.9;9.0], and the logEuroScore was 14.5 [9.0;23.0]. 30-day and one-year mortality was 5.1 % and 16.1 % for all patients, respectively. Multivariate analysis revealed that patients with NT-proBNP levels higher than two times above the upper level of normal (ULN) had an increased risk for AKI after TAVI compared to patients with NT-proBNP levels < 2× ULN (OR 1.40 [1.03–1.91]). Routine assessment of baseline NT-proBNP levels might be an additional tool to identify patients at increased risk for AKI after TAVI. • Acute kidney injury is associated with adverse outcomes in TAVI patients. • Baseline NT-proBNP is an independent predictor of AKI after TAVI. • Early identification of patients at high risk for AKI is crucial. • High-risk patients may benefit from further reducing the periprocedural amount of CM. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) during hospitalization is associated with increased complications and mortality. Despite efforts to standardize AKI management, its recognition in clinical practice is limited. Methods To assess and characterize different patterns of AKI diagnosis, we collected clinical data, serum creatinine (sCr) levels, comorbidities and outcomes from adult patients using the Hospital Discharge Form (HDF). AKI diagnosis was based on administrative data and according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria by evaluating sCr variations during hospitalization. Additionally, patients were categorized based on the timing of AKI onset. Results Among 56 820 patients, 42 900 (75.5%) had no AKI, 1893 (3.3%) had AKI diagnosed by sCr changes and coded in the HDF (full-AKI), 2529 (4.4%) had AKI reported on the HDF but not meeting sCr-based criteria (HDF-AKI) and 9498 (16.7%) had undetected AKI diagnosed by sCr changes but not coded in the HDF (KDIGO-AKI). Overall, AKI incidence was 24.5%, with a 68% undetection rate. Patients with KDIGO-AKI were younger and had a higher proportion of females, lower comorbidity burden, milder AKI stages, more frequent admissions to surgical wards and lower mortality compared with full-AKI patients. All AKI groups had worse outcomes than those without AKI, and AKI, even if undetected, was independently associated with mortality risk. Patients with AKI at admission had different profiles and better outcomes than those developing AKI later. Conclusions AKI recognition in hospitalized patients is highly heterogeneous, with a significant prevalence of undetection. This variability may be affected by patients' characteristics, AKI-related factors, diagnostic approaches and in-hospital patient management. AKI remains a major risk factor, emphasizing the importance of ensuring proper diagnosis for all patients. [ABSTRACT FROM AUTHOR]

Background: Neonatal acute kidney injury (AKI) is a common yet underdiagnosed condition in neonates with significant implications for long-term kidney health. Lack of timely recognition and documentation of AKI contributes to missed opportunities for nephrology consultation and follow-up, potentially leading to adverse outcomes. Methods: We conducted a quality improvement (QI) project to address this by incorporating an automated real-time electronic medical record (EMR)-AKI alert system in the Neonatal Intensive Care Unit (NICU) at Le Bonheur Children's Hospital. Our primary objective was to improve documentation of neonatal AKI (defined as serum creatinine (SCr) > 1.5 mg/dL) by 25% compared to baseline levels. The secondary goal was to increase nephrology consultations and referrals to the neonatal nephrology clinic. We designed an EMR-AKI alert system to trigger for neonates with SCr > 1.5 mg/dL, automatically adding AKI diagnosis to the problem list. This prompted physicians to consult nephrology, refer neonates to the nephrology clinic, and consider medication adjustments. Results: Our results demonstrated a significant improvement in AKI documentation after implementing the EMR-AKI alert, reaching 100% compared with 7% at baseline (p < 0.001) for neonates with SCr > 1.5 mg/dL. Although the increase in nephrology consultations was not statistically significant (p = 0.5), there was a significant increase in referrals to neonatal nephrology clinics (p = 0.005). Conclusions: Integration of an EMR alert system with automated documentation offers an efficient and economical solution for improving neonatal AKI diagnosis and documentation. This approach enhances healthcare provider engagement, streamlines workflows, and supports QI. Widespread adoption of similar approaches can lead to improved patient outcomes and documentation accuracy in neonatal AKI care. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19, caused by the SARS-CoV-2 virus, has been associated with oligosymptomatic cases or severe acute respiratory syndrome, with multiple organ failure and death. One of the most significant events for clinical outcomes is Acute Kidney Injury (AKI). It is known that AKI in COVID-19 is multifactorial, and the main mechanisms are cytokine storm, metabolic stress, use of nephrotoxic drugs, rhabdomyolysis, viral tropism to kidney tissues, and multiple organ failure. However, little is known about the impact of AKI clinical presentation and pathophysiological mechanisms on the outcome of patients affected by COVID-19. Objectives: To identify AKI clinical presentation and etiology, also known as phenotypes, and pathophysiological mechanisms, also known as subphenotypes, in patients affected by COVID-19 and associate them with death. This cohort and retrospective study evaluate the medical records of patients with SARS-CoV-2 infection admitted to a tertiary public hospital from 1 June 2020, to 31 July 2021, from admission to clinical outcome (hospital discharge or death). Clinical and laboratory data were analyzed during the hospitalization. Renal function was estimated by urine output and serum creatinine; therefore, the diagnosis and AKI classification were based on the 2012 KDIGO criteria. The occurrence of AKI was the inclusion criterion. According to clinical and laboratory presentations, we recognized two phenotypes of AKI (the direct and indirect impact of SARS-CoV-2 on the kidney) and several pathophysiological mechanisms. Subphenotypes of the direct impact of SARS-CoV-2 on kidneys were associated with Kidney Viral Tropism, Cytokine Storm, COVID-19-Related Multiple Organ Failure, and Mixed (more than one mechanism associated with COVID-19). Subphenotypes of indirect impact of SARS-CoV-2 on kidney phenotypes were Ischemic, Nephrotoxic due to rhabdomyolysis, and Septic. Univariate and multivariate analyses were performed to identify risk factors associated with death. Result: In total, 372 patients were included; 55.6% were male, 82.3% were Caucasians, and the mean age was 61.4 years. The majority of patients were admitted to the ICU (88.2%) and required mechanical ventilation (86.3%). AKI was predominantly KDIGO 3 (65.6%). When classifying our patients' AKI in two kidney phenotypes based on their clinical presentation, the direct impact of the SARS-CoV-2 phenotype was predominant (71,5%) and associated with higher mortality (83.8 vs. 46.3%, p = 0.001). Among the AKI pathophysiological mechanisms, Mixed—synergism of viral mechanisms—was the most prevalent (23.4%), followed by Viral Tropism (19.9%), Multiple Organ Failure—MOF (18%), Septic (15.6%), Ischemic (12.9%), and Cytokine Storm (10.2%). Mortality was high (73.1%). Logistic regression identified APACHE II, ATN-ISS, and the direct impact of SARS-CoV-2 on the kidney as factors associated with death, while ischemic AKI was associated with lower mortality. Conclusions: We can conclude that APACHE II and ATN-ISS scoring are clinical predictions of hospital mortality in COVID patients with AKI, as well as AKI etiology involving the direct impact of SARS-CoV-2 on the kidney, while ischemic pathophysiological mechanisms of AKI are associated with lower mortality. [ABSTRACT FROM AUTHOR]

Through improved insights into the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy still does not exist. Finding one is complicated by a multifactorial pathophysiology and by heterogeneity in the patient population. Alkaline phosphatase (ALP) has been suggested as a therapy for sepsis-associated AKI because of its protective effects against lipopolysaccharide (LPS)-induced inflammation and kidney injury in animals. However, its effectiveness as an AKI treatment has not been demonstrated definitively. Because the anti-inflammatory properties of ALP are likely not reliant on a direct effect on LPS itself, we postulate that other pathways are much more important in explaining the renoprotective properties ascribed to ALP. The re-evaluation of which properties of the ALP enzyme are responsible for the benefit seen in the lab is an important step in determining where the true potential of ALP as a treatment strategy for AKI in the clinic lies. In this review we will discuss how ALP can prevent activation of harmful pro-inflammatory receptors, redirect cell–cell signalling and protect barrier tissues, which together form the basis for current knowledge of the role of ALP in the kidney. With this knowledge in mind and by analysing currently available clinical evidence, we propose directions for new research that can determine whether ALP as a treatment strategy for AKI has a future in the clinical field. [ABSTRACT FROM AUTHOR]

Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney injury induced by HFRS, we measured specific markers in urine samples of patients with acute Puumala virus (PUUV) infection and determined their correlation with disease severity. Levels of α1-microglobulin (α1-MG) and kidney injury molecule 1 (KIM-1), which is expressed by injured tubular epithelial cells, were measured to detect tubular dysfunction and injury. Immunoglobulin G (IgG) and the podocyte specific protein nephrin served as markers for glomerular injury. All four markers were elevated on admission. Markers of glomerular injury, IgG and nephrin, correlated with markers of disease severity such as length of hospitalization, serum creatinine, and proteinuria. In contrast, tubular injury did not correlate with these severity markers. Our results demonstrate that hantavirus infection induces both glomerular and tubular injury early in the clinical course. However, the glomerular dysfunction and podocyte injury seem to contribute directly to disease severity and to play a more central role in HFRS pathogenicity than direct damage to tubular epithelial cells. [ABSTRACT FROM AUTHOR]

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Acute kidney injury (AKI) is a serious postoperative complication associated with increased morbidity and mortality. Identifying patients at risk for AKI is important for risk stratification and management. This study aimed to develop an AKI risk prediction model for colectomy and determine if the operative approach (laparoscopic versus open) alters the influence of predictive factors through an interaction term analysis. The American College of Surgeons National Surgical Quality Improvement Program database was analyzed from 2005 to 2019. Patients undergoing laparoscopic and open colectomy were identified and propensity score matched. Multivariable logistic regression identified significant preoperative demographic, comorbidity, and laboratory value predictors of AKI. The predictive ability of a baseline model consisting of these variables was compared to a proposed model incorporating interaction terms between operative approach and predictor variables using the likelihood ratio test, c-statistic, and Brier score. Shapley Additive Explanations values assessed relative importance of significant predictors. 252,372 patients were included in the analysis. Significant AKI predictors were hypertension, age, sex, race, body mass index, smoking, diabetes, preoperative sepsis, Congestive heart failure, preoperative creatinine, preoperative albumin, and operative approach (P < 0.001). The proposed model with interaction terms had improved predictive ability per the likelihood ratio test (P < 0.05) but had no statistically significant interaction terms. C-statistic and Brier scores did not improve. Shapley Additive Explanations analysis showed hypertension had the highest importance. The importance of age and diabetes showed some variation between operative approaches. While the inclusion of interaction terms collectively improved AKI prediction, no individual operative approach interaction terms were significant. Including operative approach interactions may enhance predictive ability of AKI risk models for colectomy. [ABSTRACT FROM AUTHOR]

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell–cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity, as well as increased medical expenses. The molecular mechanisms underlying ischemia-reperfusion (I/R)-induced AKI remain unclear. Methods and Results: We applied an RT-qPCR assay to measure the expression of mmu-lncRNA129814, hsa-lncRNA582795, and miRNA-494-5p, immunoblotting to detect IL-1α and cleaved caspase-3 expression, and TUNEL staining and flow cytometry (FCM) to evaluate apoptosis. The experiments were conducted using BUMPT and HK-2 cells, as well as C57BL/6J mice. Mechanistically, mmu-lncRNA129814 could sponge miRNA-494-5p and upregulate IL-1α expression to promote cell apoptosis. Furthermore, knockdown of mmu-lncRNA129814 ameliorated I/R-induced progression of AKI by targeting the miRNA-494-5p/IL-1α pathways. Interestingly, hsa-lncRNA582795, a homolog of mmu-lncRNA129814, also promoted I/R-stimulated HK-2 cell apoptosis and AKI progression by regulating the miRNA-494-5p/IL-1α axis. Finally, we found that patients with I/R-induced AKI exhibited significantly elevated plasma and urinary levels of hsa-lncRNA582795 compared to those who underwent ischemia-reperfusion without developing AKI. Spearman's test demonstrated a significant correlation between serum creatinine and plasma hsa-lncRNA582795 in I/R patients. Plasma hsa-lncRNA582795 showed high sensitivity but low specificity (86.7%) compared to urinary hsa-lncRNA582795. Conclusion: The mmu-lncRNA129814/hsa-lncRNA582795/miRNA-494-5p/IL-1α axis was found to modulate the progression of ischemic AKI, and hsa-lncRNA582795 could act as a diagnosis biomarker and potential therapy target of I/R-induced AKI. [ABSTRACT FROM AUTHOR]

Background and Aims: The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase‐associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study. Methods: Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL‐0) and 24 h after (NGAL‐24). Similar analysis of C‐reactive protein (CRP) was performed for additional comparison. Results: Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL‐0 (164 vs. 95 ng/mL; p < 0.001) and NGAL‐24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL‐0 and NGAL‐24 were similar within the AKI and non‐AKI groups. Using ROC curve analysis, NGAL‐0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80–0.96), compared with NGAL‐24 (0.783, 95% CI 0.74–0.85), CRP‐0 (0.701, 95% CI 0.58–0.83), and CRP‐24 (0.781, 95% CI 0.66–0.90). The optimal NGAL‐0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value. Conclusions: Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI. [ABSTRACT FROM AUTHOR]

Background: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety. Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis. Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L. Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mortality is high within the first few months of starting chronic dialysis. Pre-ESKD trajectory of kidney function has been shown to be predictive of early death after dialysis initiation. We aim to better understand how two key aspects of pre-dialysis kidney function-an abrupt transition pattern and an episode of dialysis-requiring AKI (AKI-D) leading directly to ESKD-are associated with early mortality after dialysis initiation. METHODS: We extracted national data from U.S. Veterans Health Administration cross-linked with the United States Renal Data System (USRDS) to identify patients who initiated hemodialysis during 2009-2013. We defined abrupt transition as having a mean outpatient eGFR ≥ 30 ml/min/1.73m2 within 1 year prior to ESKD. AKI-D was identified using inpatient serum creatinine measurements (serum Cr increase by at least 50% from baseline) along with billing codes for inpatient receipt of dialysis for AKI within 30 days prior to the ESKD start date. We used multivariable proportional hazards models to examine the association between patterns of kidney function prior to ESKD and all-cause mortality within 90 days after ESKD. RESULTS: Twenty-two thousand eight hundred fifteen patients were identified in the final analytic cohort of Veterans who initiated hemodialysis and entered the USRDS. We defined five patterns of kidney function decline. Most (68%) patients (N = 15,484) did not have abrupt transition and did not suffer an episode of AKI-D prior to ESKD (reference group). The remaining groups had abrupt transition, AKI-D, or both. Patients who had an abrupt transition with (N = 503) or without (N = 3611) AKI-D had the highest risk of early mortality after ESKD onset after adjustment for demographics and comorbidities (adjusted HR 2.10, 95% CI 1.66-2.65 for abrupt transition with AKI-D; adjusted HR 2.10, 95% CI 1.90-2.33 for abrupt transition without AKI-D). In contrast, patients who experienced AKI-D without an abrupt transition pattern (N =  2141 had only a modestly higher risk of early death (adjusted HR 1.19, 95% CI 1.01-1.40). CONCLUSIONS: An abrupt decline in kidney function within 1 year prior to ESKD occurred in nearly 1 in 5 incident hemodialysis patients (18%) in this national cohort of Veterans and was strongly associated with higher early mortality after ESKD onset.

Introduction: COVID-19, caused by the SARS-CoV-2 virus, has been associated with oligosymptomatic cases or severe acute respiratory syndrome, with multiple organ failure and death. One of the most significant events for clinical outcomes is Acute Kidney Injury (AKI). It is known that AKI in COVID-19 is multifactorial, and the main mechanisms are cytokine storm, metabolic stress, use of nephrotoxic drugs, rhabdomyolysis, viral tropism to kidney tissues, and multiple organ failure. However, little is known about the impact of AKI clinical presentation and pathophysiological mechanisms on the outcome of patients affected by COVID-19. Objectives: To identify AKI clinical presentation and etiology, also known as phenotypes, and pathophysiological mechanisms, also known as subphenotypes, in patients affected by COVID-19 and associate them with death. This cohort and retrospective study evaluate the medical records of patients with SARS-CoV-2 infection admitted to a tertiary public hospital from 1 June 2020, to 31 July 2021, from admission to clinical outcome (hospital discharge or death). Clinical and laboratory data were analyzed during the hospitalization. Renal function was estimated by urine output and serum creatinine; therefore, the diagnosis and AKI classification were based on the 2012 KDIGO criteria. The occurrence of AKI was the inclusion criterion. According to clinical and laboratory presentations, we recognized two phenotypes of AKI (the direct and indirect impact of SARS-CoV-2 on the kidney) and several pathophysiological mechanisms. Subphenotypes of the direct impact of SARS-CoV-2 on kidneys were associated with Kidney Viral Tropism, Cytokine Storm, COVID-19-Related Multiple Organ Failure, and Mixed (more than one mechanism associated with COVID-19). Subphenotypes of indirect impact of SARS-CoV-2 on kidney phenotypes were Ischemic, Nephrotoxic due to rhabdomyolysis, and Septic. Univariate and multivariate analyses were performed to identify risk factors associated with death. Result: In total, 372 patients were included; 55.6% were male, 82.3% were Caucasians, and the mean age was 61.4 years. The majority of patients were admitted to the ICU (88.2%) and required mechanical ventilation (86.3%). AKI was predominantly KDIGO 3 (65.6%). When classifying our patients’ AKI in two kidney phenotypes based on their clinical presentation, the direct impact of the SARS-CoV-2 phenotype was predominant (71,5%) and associated with higher mortality (83.8 vs. 46.3%, p = 0.001). Among the AKI pathophysiological mechanisms, Mixed—synergism of viral mechanisms—was the most prevalent (23.4%), followed by Viral Tropism (19.9%), Multiple Organ Failure—MOF (18%), Septic (15.6%), Ischemic (12.9%), and Cytokine Storm (10.2%). Mortality was high (73.1%). Logistic regression identified APACHE II, ATN-ISS, and the direct impact of SARS-CoV-2 on the kidney as factors associated with death, while ischemic AKI was associated with lower mortality. Conclusions: We can conclude that APACHE II and ATN-ISS scoring are clinical predictions of hospital mortality in COVID patients with AKI, as well as AKI etiology involving the direct impact of SARS-CoV-2 on the kidney, while ischemic pathophysiological mechanisms of AKI are associated with lower mortality.

Acute kidney injury (AKI) has become increasingly prevalent in both resource rich and resource poor countries and is associated with significantly higher morbidity and mortality in the later, where access to renal replacement therapy (RRT) is poor. Peritoneal Dialysis (PD) is a well acknowledged and established form of RRT and it appears to be the most practical modality in young children with AKI in such countries. PD, though a cheaper alternative to haemodialysis (HD), is still challenging and unaffordable due to complex problems like lack of standard PD catheters and dialysate fluid, poor access to health facilities for rural dwellers, late presentations to health facilities and pervasive poverty. With some ingenuity, cheaper and more widely available alternatives like improvised catheters e.g. nasogastric tube, rubber catheter, intercostal drainage catheter, haemodialysis catheters and self-constituted fluid e.g. fortified ringers lactate, 0.9% sodium chloride with modified sodium lactate can been used with success. In this article, we share our experience on how acute PD was carried out successfully in a five-year old male with AKI complicated by uraemic encephalopathy, using improvised peritoneal dialysis and self-constituted PD solution in a place where standard renal replacement therapy does not exist.

Acute kidney injury (AKI) is one of the most common and severe clinical syndromes of diffuse proliferative lupus nephritis (DPLN), of which poor prognosis is indicated by aggravated renal function deterioration. However, the specific therapy and mechanisms of AKI in DPLN remain to be explored. The correlation between AKI and clinical pathological changes in DPLN patients was analyzed. Expression of STAT3 signaling was detected in MRL/lpr mice with DPLN using immunohistochemical staining and immunoblotting. Inhibition of STAT3 activation by combination therapy was assessed in MRL/lpr mice. Correlation analysis revealed only the interstitial leukocytes were significantly related to AKI in endocapillary DPLN patients. MRL/lpr mice treated with vehicle, which can recapitulate renal damages of DPLN patients, showed upregulation of STAT3, pSTAT3 and caspase-1 in renal cortex. FLLL32 combined with methylprednisolone therapy significantly inhibited the STAT3 activation, improved acute kidney damage, reduced the interstitial infiltration of inflammatory cells and decreased the AKI incidence in MRL/lpr mice. STAT3 activation may play an important role in the pathogenesis of DPLN and the development of AKI. Hence, STAT3 inhibition based on the combination of FLLL32 with methylprednisolone may represent a new strategy for treatment of DPLN with AKI. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence. [ABSTRACT FROM AUTHOR]

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment. [ABSTRACT FROM AUTHOR]

Predicting the successful weaning of acute kidney injury (AKI) patients from renal replacement therapy (RRT) has emerged as a research focus, and we successfully built predictive models for RRT withdrawal in patients with severe AKI by machine learning. This retrospective single-center study utilized data from our general intensive care unit (ICU) Database, focusing on patients diagnosed with severe AKI who underwent RRT. We evaluated RRT weaning success based on patients being free of RRT in the subsequent week and their overall survival. Multiple logistic regression (MLR) and machine learning algorithms were adopted to construct the prediction models. A total of 976 patients were included, with 349 patients successfully weaned off RRT. Longer RRT duration (7.0 vs. 9.6 d, p = 0.002, OR = 0.94), higher serum cystatin C levels (1.2 vs. 3.2 mg/L, p < 0.001, OR = 0.46), and the presence of septic shock (28.1% vs. 41.5%, p < 0.001, OR = 0.63) were associated with reduced likelihood of RRT weaning. Conversely, a positive furosemide stress test (FST) (60.2% vs. 40.7%, p < 0.001, OR = 2.75) and higher total urine volume 3 d before RRT withdrawal (755 vs. 125 mL/d, p < 0.001, OR = 2.12) were associated with an increased likelihood of successful weaning from RRT. Next, we demonstrated that machine learning models, especially Random Forest and XGBoost, achieving an AUROC of 0.95. The XGBoost model exhibited superior accuracy, yielding an AUROC of 0.849. High-risk factors for unsuccessful RRT weaning in severe AKI patients include prolonged RRT duration. Machine learning prediction models, when compared to models based on multivariate logistic regression using these indicators, offer distinct advantages in predictive accuracy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the correlation of different methods of assessing fluid overload and determine which metrics are associated with development of acute kidney injury (AKI) in the period immediately following Norwood palliation. This was a retrospective single-center study of Norwood patients from January 2011 through January 2021. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO). Patients were separated into two groups: those with AKI and those without. A logistic regression analysis was conducted with AKI at any point in the study period as the dependent variable and clinical and laboratory data as independent variables. Analysis was conducted as a stepwise regression. The coefficients from the logistic regression were then used to develop a cumulative AKI risk score. Spearman correlations were conducted to analyze the correlation of fluid markers. 116 patients were included, and 49 (42.4%) developed AKI. The duration of open chest, duration of mechanical ventilation, need for dialysis, need for extracorporeal membrane oxygenation, and inpatient mortality were associated with AKI (p ≤ 0.05). Stepwise logistic regression demonstrated the following significant independent associations AKI: age at Norwood in days (p < 0.01), blood urea nitrogen (p < 0.01), central venous pressure (p = 0.04), and renal oxygen extraction ratio (p < 0.01). The area under the receiver operating characteristic curve for the logistic regression was 0.74. The fluid markers had weak R-value. Urea, central venous pressure, and renal oxygen extraction ratio are associated with AKI after the Norwood operation. Common clinical metrics used to assess fluid overload are poorly correlated with each other for postoperative Norwood patients. [ABSTRACT FROM AUTHOR]

Advanced glycation endproducts (AGEs) contribute to cellular damage of various pathologies, including kidney diseases. Acute kidney injury (AKI) represents a syndrome seldom characterized by a single, distinct pathophysiological cause. Rhabdomyolysis-induced acute kidney injury (RIAKI) constitutes roughly 15% of AKI cases, yet its underlying pathophysiology remains poorly understood. Using a murine model of RIAKI induced by muscular glycerol injection, we observed elevated levels of AGEs and the AGE receptor galectin-3 (LGALS3) in the kidney. Immunofluorescence localized LGALS3 to distal nephron segments. According to transcriptomic profiling via next-generation sequencing, RIAKI led to profound changes in kidney metabolism, oxidative stress, and inflammation. Cellular stress was evident in both proximal and distal tubules, as shown by kidney injury markers KIM-1 and NGAL. However, only proximal tubules exhibited overt damage and apoptosis, as detected by routine morphology, active Caspase-3, and TUNEL assay, respectively. In vitro, distal convoluted tubule (DCT) cells challenged with AGEs underwent apoptosis, which was markedly enhanced by Lgals3 siRNA treatment. Thus, in RIAKI, the upregulation of LGALS3 may protect the distal nephron from AGE-mediated damage, while proximal tubules lacking LGALS3 stay at risk. Thus, stimulating LGALS3 in the proximal nephron, if achievable, may attenuate RIAKI. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors. Methods: This is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients. Results: Patterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis. Conclusions: Our case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition. [ABSTRACT FROM AUTHOR]

Abstract Background The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P

Abstract Background Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. Methods Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). Results A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. Conclusion The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

Abstract Background Chronic kidney disease (CKD) is a common postoperative complication in patients who undergo radical nephrectomy for renal tumours. However, the factors influencing long-term renal function require further investigation. Objective This study was designed to investigate the trends in renal function changes and risk factors for renal function deterioration in renal tumour patients after radical nephrectomy. Methods We monitored changes in renal function before and after surgery for 3 years. The progression of renal function was determined by the progression and degradation of CKD stages. Univariate and multivariate logistic regression analyses were used to analyse the causes of renal function progression. Results We analysed the data of 329 patients with renal tumours who underwent radical nephrectomies between January 2013 and December 2018. In this study, 43.7% of patients had postoperative acute kidney injury (AKI), and 48.3% had CKD at advanced stages. Further research revealed that patients’ renal function stabilized 3 months after surgery. Additionally, renal function changes during these 3 months have a substantial impact on the progression of long-term renal function changes in patients. Conclusion AKI may be an indicator of short-term postoperative changes in renal function. Renal function tests should be performed in patients with AKI after radical nephrectomy to monitor the progression of functional impairment, particularly within the first 3 months after radical nephrectomy.

Abstract Background Serum lactate is associated with mortality in diverse kinds of patients. This study aimed to investigate whether serum lactate level may independently predict mortality in acute kidney injury (AKI) patients. Methods A total of 4461 AKI patients were collected from the Medical Information Mart for Intensive Care (MIMIC III) database and followed up for 365 days. According to serum lactate tertiles, participants were divided into three groups (Q1–Q3) by: Q1 ≤ 1.60 mg/dl, Q2 = 1.61–2.70 mg/dl, and Q3 ≥ 2.71 mg/dl. We calculated the hazard ratio (HR) and 95% confidence intervals (Cls) for mortality across each tertile of lactate by using the Q1 as reference and constructed four models to adjust for the HR of mortality. Results Nonsurvivors had significantly higher lactate compared with patients in the survival group. Mortality rate gradually elevated with the increase in serum lactate level (Q1: 29.30%, Q2: 33.40%, Q3: 37.40%). When compared with Q1 after adjustment of all confounders, the HRs of Q3 still was 1.20 (95% Cl 1.05–1.37). Conclusions This study demonstrated that high serum lactate levels were an independent predictor of mortality in AKI patients.

Abstract Background Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. Methods We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. Results Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr

Abstract Background Preliminary studies suggest that moderate ARDS and acute renal failure might benefit from extracorporeal CO2 removal (ECCO2R) coupled with CRRT. However, evidence is limited and potential for this coupled treatment may need to be explored. The aim of the present study was to evaluate whether a protective driving pressure was obtained applying low-flow ECCO2-R plus CRRT in patients affected by moderate ARDS with COVID-19 compared to an historical group without COVID-19. Methods A case-control study has been conducted comparing a group of consecutive moderate ARDS patients presenting AKI and affected by COVID-19, who needed low-flow ECCO2-R plus CRRT to achieve an ultra-protective ventilatory strategy, with historical group without COVID-19 that matched for clinical presentation and underwent the same ultra-protective treatment. VT was set at 6 mL/kg predicted body weight then ECCO2R was assessed to facilitate ultra-protective low VT ventilation to preserve safe Pplat and low driving pressure. Results ECCO2R+CRRT reduced the driving pressure from 17 (14-18) to 11.5 (10-15) cmH2O (p

Background: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods: We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result: The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P < 0.001). After adjusting for potential confounding variables, the multivariable regression analysis showed that the flurbiprofen group had a 49% reduced risk of postoperative AKI (OR 0.51; 95% CI 0.31 to 0.82) compared to the non-flurbiprofen group. Subgroup analysis indicated that flurbiprofen injection was associated with a reduced incidence of postoperative AKI in patients without diabetes (OR 0.61; 95% CI 0.19 to 0.74), surgical times of 2–5 h (OR 0.54; 95% CI 0.23 to 0.75), and preoperative anemia (OR 0.57; 95% CI 0.21 to 0.74). Conclusion: The study concluded that perioperative flurbiprofen treatment was associated with a lower risk of postoperative AKI in adult patients undergoing spinal surgery. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher (p < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. Methods: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). Results: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. Conclusion: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making. [ABSTRACT FROM AUTHOR]

Background and Aims: Terlipressin infusion is effective in hepatorenal syndrome (HRS-AKI). However, its efficacy for HRS-AKI resolution in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF. We investigated whether early initiation of terlipressin(eTerli) can improve response rates. Methods: Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40 g) were randomized to receive terlipressin at 2 mg/24 h plus albumin at 12 h (ET, n = 35) or at 48 h as standard therapy (ST, n = 35). (June 22, 2020 to June 10, 2022). The primary end-point was AKI reversal by day7. Results: Baseline parameters including AKI stage and ACLF-AARC scores in two arms were comparable. Full AKI response at day 7 was higher in ET [24/35 (68.6%)] than ST arm [11/35 (31.4%; P 0.03]. Day3 AKI response was also higher in ET arm [11/35 (31.4%) vs. 4/35 (11.4%), P 0.04]. Using ST compared to ET [HR 4.3; P 0.026] and day 3 serum creatinine > 1.6 mg/dl [HR 9.1; AUROC-0.866; P < 0.001] predicted HRS-AKI non-response at day 7. ET patients showed greater improvement in ACLF grade, mean arterial pressure, and urine output at day 3, and required lower albumin within 7 days than ET arm (149.1 ± 41.8 g vs. 177.5 ± 40.3 g, P 0.006) and had lower 28-day mortality: 40% vs. 65.7%, P 0.031]. Early use of terlipressin than ST [HR 2.079; P 0.038], baseline HE [HR 2.929; P 0.018], and AKI persistence at day 3 [HR 1.369; P 0.011] predicted 28-day mortality. Fifteen (21.4%) patients had treatment related adverse effects, none was life threatening. Conclusion: In ACLF patients, early initiation of terlipressin for AKI persisting after 12 h of volume expansion with albumin helps in reduced short-term mortality and early AKI reversal with regression of ACLF stage. These results indicate need for change in current practice for terlipressin usage in HRS-AKI. [ABSTRACT FROM AUTHOR]