Factors predicting acute kidney injury in patients after abdominal aortic aneurysm repair.

INTRODUCTION: Postoperative acute kidney injury (AKI) is one of the most frequent complications in abdominal aortic aneurysm (AAA) patients after open and endovascular aortic aneurysm repair. AKI decreases the efficiency of kidney function, allowing accumulation of waste products in the body, and an imbalance of water, acid and electrolytes in the body. As a result, the functioning of various organs throughout the body is affected. These effects may raise the cost of treatment, length of stay, and mortality rate. OBJECTIVE: This study aims to examine the predictive factors of AKI - preoperative of estimated glomerular filtration rate (eGFR), preoperative of hemoglobin level, types of abdominal aortic aneurysms repair, and intraoperative of cardiac arrhythmias - after open and endovascular aortic repair among AAA patients within 72 h. METHODS: This is a retrospective study of 196 patients with AAA after elective open and endovascular aortic aneurysm repair within the first 72 h who met the inclusion criteria recruited from a tertiary care hospital in Bangkok, Thailand. Postoperative AKI after elective open and endovascular aortic repair among AAA patients is defined by the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines. RESULTS: A total of 196 AAA patients, 75.5% were male with an average age of 75.12 years (SD = 8.45). Endovascular aortic aneurysm repair was used more frequently than open aortic aneurysm repair (64.8% vs 35.2%) and 37.2% of the AAA patients had intraoperative cardiac arrhythmias. The occurrence of AKI among the AAA patients after abdominal aortic aneurysm repair within 72 h was 54.1%. The AKI rate of EVAR patients was 69.8% while the AKI rate for OAR patients was 30.2%. The preoperative estimated glomerular filtration rate (eGFR) and hemoglobin level were found to jointly predict AKI and explain 32.2% of the variance (Nagelkerke R2 = 0.322, p < .05). However, the type of abdominal aortic aneurysms repair and intraoperative cardiac arrhythmias did not correlate with the incidence of AKI in AAA repair patients. The predictive factors for AKI among AAA patients after aortic aneurysm repair were preoperative eGFR < 60 mL/min/1.73 m2 (OR = 4.436, 95% CI: 2.202-8.928, p < .001) and preoperative hemoglobin level between 8.1-10.0 g/dL (OR = 4.496, 95% CI: 1.831-11.040, p = .001). CONCLUSION: Preoperative eGFR < 60 mL/min/1.73 m2 and preoperative hemoglobin level between 8.1-10.0 g/dL were the predictive factors for AKI among AAA patients after both open and endovascular AAA repair. Therefore, healthcare providers should be aware of and monitor signs of AKI after surgery in AAA patients, especially those undergoing EVAR with lower eGFR and hemoglobin levels.

TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2-/- mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2-/- BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-ß1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Predictive approach for liberation from acute dialysis in ICU patients using interpretable machine learning.

Renal recovery following dialysis-requiring acute kidney injury (AKI-D) is a vital clinical outcome in critical care, yet it remains an understudied area. This retrospective cohort study, conducted in a medical center in Taiwan from 2015 to 2020, enrolled patients with AKI-D during intensive care unit stays. We aimed to develop and temporally test models for predicting dialysis liberation before hospital discharge using machine learning algorithms and explore early predictors. The dataset comprised 90 routinely collected variables within the first three days of dialysis initiation. Out of 1,381 patients who received acute dialysis, 27.3% experienced renal recovery. The cohort was divided into the training group (N = 1135) and temporal testing group (N = 251). The models demonstrated good performance, with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81-0.88) and an area under the precision-recall curve of 0.69 (95% CI, 0.62-0.76) for the XGBoost model. Key predictors included urine volume, Charlson comorbidity index, vital sign derivatives (trend of respiratory rate and SpO2), and lactate levels. We successfully developed early prediction models for renal recovery by integrating early changes in vital signs and inputs/outputs, which have the potential to aid clinical decision-making in the ICU.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Multicentre, retrospective cohort study protocol to identify racial and ethnic differences in acute kidney injuries in children and adolescents with diabetic ketoacidosis.

INTRODUCTION: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA. METHODS AND ANALYSIS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is 'sustained' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering. ETHICS AND DISSEMINATION: The Institutional Review Board of Children's Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

Effects of Cognitive Behavioural Therapy on Mental Health and Sleep in Acute Kidney Injury Patients with Ureteral Calculi in the Emergency Department: A Retrospective Study.

BACKGROUND: Acute kidney injury (AKI) resulting from ureteral stones in the emergency department is typically accompanied with anxiety and sleep issues in patients, which can have adverse effects on their mental health and quality of life. Cognitive behavioural therapy (CBT) is helpful in improving mental health and sleep. This work aims to analyse the effects of CBT on mental health and sleep of AKI patients caused by ureteral calculi in the emergency department. METHODS: The clinical data of patients with AKI caused by ureteral calculi in the emergency department of our hospital from February 2021 to February 2023 were retrospectively analyzed. The patients were divided into the control group (routine nursing) and observation group (cognitive behavioural nursing) according to the different nursing methods of data recording. Propensity Score Matching (PSM) was used to balance the confounding factors of the two groups. After matching, the State Trait Anxiety Inventory (STAI), Insomnia Severity Index (ISI), Mishel Uncertainty in Illness Scale-Adult (MUIS) and 36-Item Short-Form Health Survey (SF-36) were compared between the two groups. RESULTS: After matching at a ratio of 1:1, 130 patients were included in the observation group and the control group, with 65 cases in each group. No significant difference was observed in STAI, ISI, MUIS and SF-36 scores between the two groups before nursing (p > 0.05). After nursing, the STAI, ISI and MUIS scores of the observation group were lower than those of the control group (p < 0.05). Furthermore, the SF-36 score of the observation group was higher than that of the control group (p < 0.05). CONCLUSIONS: Cognitive behavioural nursing for patients with AKI caused by ureteral calculi in the emergency department may help in retrieving patients' anxiety, reducing the severity of disease uncertainty and insomnia, improving the quality of life of patients and providing theoretical reference for clinical practice.

Impact of Tolvaptan Combined with Low-Dose Dopamine in Heart Failure Patients with Acute Kidney Injury.

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 µg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

Late Kidney Injury After Admission to Intensive Care Unit for Acute Heart Failure.

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

[Association between onset time of sepsis-associated acute kidney injury and clinical outcome in patients with sepsis].

Objective: To explore the relationship between the onset time of sepsis-associated acute kidney injury (SA-AKI) and adverse clinical outcomes. Methods: Data were derived from Beijing Acute Kidney Injure Trial (BAKIT) which investigated the epidemiology of acute kidney injury (AKI) in critically ill patients at 30 intensive care units (ICU) of 28 tertiary hospitals in Beijing from 1 March to 31 August 2012. Patients who were older than 18 years and diagnosed with sepsis and AKI, and expected to stay in ICU for at least 24 h were included in this study. A total of 653 patients were included in this study, 414 males and 239 females with a mean age of (68.2±17.0) years. According to the onset time of SA-AKI, patients were grouped into early AKI (E-AKI) (AKI occurred within 48 hours after ICU admission) and late AKI (L-AKI) (AKI occurred after 48 hours of ICU admission) group. The primary outcome was major adverse kidney events (MAKE), consisted of all-cause mortality, renal replacement therapy-dependence, and an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. Multivariable logistic regression was used to investigate the association between the onset time of SA-AKI and clinical outcomes. Results: A total of 653 patients with SA-AKI were included, 423 (64.8%) patients developed E-AKI, 230 (35.2%) cases developed L-AKI, MAKE occurred in 405 (62.0%) cases, and 301 (46.1%) patients died in hospital. Compared with E-AKI group, L-AKI patients showed higher AKI 3 level rate [55.7%(128/230) vs 40.2%(170/423), P<0.001], incidence of MAKE [72.6%(167/230) vs 56.3%(238/423,P<0.001)] and hospital mortality [55.2%(127/230) vs 44.1%(174/423), P=0.001]. The risk of MAKE and in-hospital mortality in L-AKI group increased for 2.55-fold times (OR=3.55, 95%CI: 1.94-6.04) and 1.84-fold times (OR=2.84, 95%CI: 1.44-5.60) when compared with those in E-AKI, respectively (both P<0.05). Conclusion: Late timing onset of SA-AKI is associated with poor clinical outcomes.

Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial.

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 µg kg-1 for 10 min, followed by 0.5 µg kg-1 hr-1 for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.

Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis.

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.

Development and external validation of a machine learning model for the prediction of persistent acute kidney injury stage 3 in multi-centric, multi-national intensive care cohorts.

BACKGROUND: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. RESULTS: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92-0.95) in the US external validation cohort and 0.85 (95% CI 0.83-0.88) in the Italian external validation cohort. CONCLUSIONS: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice.

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center.

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.

[Development and validation of a nomogram for predicting 3-month mortality risk in patients with sepsis-associated acute kidney injury].

OBJECTIVE: To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI). METHODS: Based on the American Medical Information Mart for Intensive Care- IV (MIMIC- IV), clinical data of S-AKI patients from 2008 to 2021 were collected. Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7 : 3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds. RESULTS: Based on the survival status at 3 months after diagnosis, patients were divided into 7 768 (68.54%) survivors and 3 566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95%CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95%CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95%CI was 0.56-0.58) and SIRS score's 0.56 (95%CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. CONCLUSIONS: A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC- IV and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.

[Predictive value of albumin-to-fibrinogen ratio for acute kidney injury in infants undergoing ventricular septal defect repair with cardiopulmonary bypass].

OBJECTIVE: To investigate the predictive value of albumin-to-fibrinogen ratio (AFR) for postoperative acute kidney injury (AKI) in infants with ventricular septal defect repair under cardiopulmonary bypass (CPB). METHODS: A retrospective analysis was conducted on infants diagnosed with ventricular septal defect in Anhui Children's Hospital from January 2019 to July 2023. The infants were divided into AKI group and non-AKI group according to whether AKI occurred in hospital after operation. Demographic data, preoperative data, intraoperative data, postoperative data and laboratory results during CPB were collected. Multivariate Logistic regression analysis was used to find the factors of AKI after ventricular septal defect repair with CPB. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of AFR for postoperative AKI after ventricular septal defect repair with CPB. RESULTS: A total of 215 children were collected, including 28 in AKI group and 187 in non-AKI group. There were no significant differences in age, gender, body weight, height, history of pneumonia and history of chronic heart failure between the two groups, but the left ventricular ejection fraction (LVEF) in the AKI group was significantly lower than that in the non-AKI group (0.526±0.028 vs. 0.538±0.030, P = 0.048). The duration of CPB (minutes: 74.1±12.1 vs. 65.8±11.3, P < 0.001), aortic cross-clamping (minutes: 41.7±9.7 vs. 37.2±9.4, P = 0.021) and hypothermic circulation arrest (21.4% vs. 8.6%, P = 0.047) in AKI group were significantly higher than those in non-AKI group, but there were no significant differences in the proportion of ultrafiltration and urine volume between the two groups. The length of intensive care unit (ICU) stay in AKI group was significantly longer than that in non-AKI group (days: 5.3±2.0 vs. 4.0±1.7, P < 0.001), but there were no significant differences in duration of mechanical ventilation and the proportion of postoperative hypotension between the two groups. During CPB, the levels of blood glucose (mmol/L: 9.4±1.3 vs. 8.8±0.8, P < 0.001), blood lactic acid (mmol/L: 2.2±0.3 vs. 2.0±0.3, P = 0.015) and serum creatinine (µmol/L: 79.7±11.5 vs. 74.4±10.9, P = 0.018) in AKI group were significantly higher than those in non-AKI group, while the AFR was significantly lower than that in non-AKI group (8.5±1.3 vs. 10.2±1.6, P < 0.001), but there were no significant differences in the levels of hemoglobin, blood urea nitrogen, alanine aminotransferase and aspartate aminotransferase between the two groups during CPB. Multivariate Logistic regression showed that AFR was a protective factor for AKI after ventricular septal defect repair with CPB [odds ratio (OR) = 0.439, 95% confidence interval (95%CI) was 0.288-0.669, P < 0.001]. Blood glucose (OR = 2.133, 95%CI was 1.239-3.672, P = 0.006) and blood lactic acid (OR = 5.568, 95%CI was 1.102-28.149, P = 0.038) were risk factors for AKI after ventricular septal defect repair with CPB. ROC curve analysis showed that the area under the curve (AUC) of AFR in predicting AKI after ventricular septal defect repair with CPB was 0.804 (95%CI was 0.712-0.897, P < 0.001). When the optimal cut-off value was less than 9.05, the corresponding sensitivity was 75.0% and the specificity was 72.7%. CONCLUSIONS: Low AFR (≤9.05) during CPB is an independent risk factor for AKI after ventricular septal defect repair with CPB. AFR during CPB has a high predictive value for postoperative AKI after ventricular septal defect repair with CPB.

H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury.

Background: Cisplatin is a commonly used nephrotoxic drug and can cause acute kidney injury (AKI). In the present study, isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM)-based comparative proteomics were used to analyze differentially expressed proteins (DEPs) to determine the key molecular mechanism in mice with cisplatin-induced AKI in the presence or absence of SIS3, a specific p-smad3 inhibitor, intervention. Methods: The cisplatin-induced AKI mouse model was established and treated with SIS3. We used iTRAQ to search for DEPs, PRM to verify key DEPs and combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for bioinformatics analysis. We then assessed lipid deposition, malondialdehyde (MDA) and reactive oxygen species (ROS) and detected the expression of SREBF1, SCD1, CPT1A, PPARα and NDRG1 in vitro. Results: Proteomic analysis showed that the identified DEPs were mainly enriched in energy metabolism pathways, especially in lipid metabolism. When SIS3 was applied to inhibit the phosphorylation of Smad3, the expression of NDRG1 and fatty acid oxidation key proteins CPT1A and PPARα increased, the expression of lipid synthesis related proteins SREBF1 and SCD1 decreased and the production of lipid droplets, MDA and ROS decreased. Conclusion: SIS3 alleviates oxidative stress, reduces lipid accumulation and promotes fatty acid oxidation through NDRG1 in cisplatin-induced AKI. Our study provides a new candidate protein for elucidating the molecular mechanisms of fatty acid metabolism disorders in cisplatin-induced acute kidney injury.

Proximal tubular dysfunction as a predictor of AKI in Hospitalized COVID-19 patients.

BACKGROUND: High concentration of Angiotensin converting enzyme receptors in the proximal tubules make kidneys an early target in COVID-19. Proximal tubular dysfunction (PTD) may act as an early predictor of acute kidney injury (AKI) and more severe disease. METHODS: This prospective observational study was conducted in the COVID unit, Bangabandhu Sheikh Mujib Medical University. 87 COVID-19 patients without known kidney disease were screened for 6 markers of PTD on admission-hyperuricosuria, normoglycemic glycosuria, proteinuria, renal phosphate leak, sodium leak and potassium leak. Positivity of 2 of the first 4 markers was considered as PTD. 35 patients with PTD and 35 without PTD were followed up throughout their hospital stay. RESULTS: 52.9% had PTD on admission. The most prevalent markers were renal sodium leak (67%), followed by proteinuria (66.7%), hyperuricosuria (42.5%), potassium leak (32.2%), phosphate leak (28.7%) and normoglycemic glycosuria (20.7%). Mean age was 55.7 years. 32.9% patients developed AKI. PTD group had higher odds of developing AKI (odds ratio 17.5 for stage 1, 24.8 for stage 2 and 25.5 for stage 3; p<0.0001). The mean duration of hospital stay was 9 days higher in the PTD group (p<0.001). PTD group also had higher odds of transferring to ICU (OR = 9.4, p = 0.002), need for mechanical ventilation (OR = 10.1, p = 0.002) and death (OR = 10.3, p = 0.001). 32.6% had complete PTD recovery during follow-up. CONCLUSION: Proximal tubular dysfunction is highly prevalent in COVID-19 patients very early in the disease and may act as a predictor of AKI, ICU transfer, need for mechanical ventilation and death.

Impact of severe acute kidney injury on short-term mortality in urosepsis.

PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.