Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery
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ABSTRACT:
SUBMITTER: Asfari A
PROVIDER: S-EPMC10560364 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:IntroductionAcute kidney injury (AKI) after cardiac surgery is independently associated with a prolonged hospital stay, increased cost of care, and increased post-operative mortality. Delayed elevation of serum creatinine (SCr) levels requires novel biomarkers to provide a prediction of AKI after cardiac surgery. Our objective was to find a novel blood biomarkers combination to construct a model for predicting AKI after cardiac surgery and risk stratification.MethodsThis was a case-control study. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to Gene Expression Omnibus (GEO) dataset GSE30718 to seek potential biomarkers associated with AKI. We measured biomarker levels in venous blood samples of 67 patients with AKI after cardiac surgery and 59 control patients in two cohorts. Clinical data were collected. We developed a multi-biomarker model for predicting cardiac-surgery-associated AKI and compared it with a traditional clinical-factor-based model.ResultsFrom bioinformatics analysis and previous articles, we found 6 potential plasma biomarkers for the prediction of AKI. Among them, 3 biomarkers, such as growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 (ST2, IL1RL1), and soluble urokinase plasminogen activator receptor (uPAR) were found to have prediction ability for AKI (area under the curve [AUC] > 0.6) in patients undergoing cardiac surgery. They were then incorporated into a multi-biomarker model for predicting AKI (C-statistic: 0.84, Brier 0.15) which outperformed the traditional clinical-factor-based model (C-statistic: 0.73, Brier 0.16).ConclusionOur research validated a promising plasma multi-biomarker model for predicting AKI after cardiac surgery.
| S-EPMC8795513 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) occurs in about 30% of patients with cardiac surgery, but the pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) remains unclear and there are no predictive biomarkers or diagnostic criteria specific for CSA-AKI beyond the general clinical variables for AKI like serum creatinine (SCr).Methods and resultsWe measured the plasma levels of 48 cytokines within 24 h after cardiac surgery in a total of 306 adult patients including 204 with and 102 without AKI, and then evaluated the diagnostic efficacy of these cytokines for the development of CSA-AKI via ANOVA and Pearson correlation analysis. Among these 48 cytokines, 20 of them were significantly different in the AKI patients compared with the non-AKI patients. In particularly, 13 cytokines displayed tremendous changes with the P < 1E-5. Moreover, 10 of the 48 cytokines in the plasma were significantly different among the patients with different stages of AKI. Specifically, 6 cytokines exhibited immense differences with the P < 1E-5. Additionally, 7 of the 48 cytokines have the correlation coefficient of r > 0.5 with the postoperative changes of SCr after cardiac surgery.ConclusionTaken all the results together, IFN-γ and SCGF-β were the most relevant two cytokines that were not only remarkably changed in adult CSA-AKI patients during the first 24 h after cardiac surgery, but also significantly correlated with the postoperative changes of SCr after cardiac surgery. Therefore, IFN-γ and SCGF-β might be novel predictive plasma biomarker, as well as potential therapeutic targets specific for adult CSA-AKI.
| S-EPMC7683426 | biostudies-literature
Project description:IntroductionAcute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).MethodsConsecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation.ResultsFifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001).ConclusionsElevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.
| S-EPMC3580637 | biostudies-literature
Project description:Acute kidney injury (AKI) in the pediatric population is a relatively common phenomenon. Specifically, AKI has been found in increasing numbers within the pediatric population following cardiac surgery, with up to 43% of pediatric patients developing AKI post-cardiac surgery. However, recent advances have allowed for the identification of risk factors. These can be divided into preoperative, intraoperative, and postoperative factors. Although the majority of pediatric patients developing AKI after cardiac surgery completely recover, this condition is associated with worse outcomes. These include fluid overload and increased mortality and result in longer hospital and intensive care unit stays. Detecting the presence of AKI has advanced; use of relatively novel biomarkers, including neutrophil gelatinase associated lipocalin, has shown promise in detecting more subtle changes in kidney function when compared to conventional methods. While a single, superior treatment has not been elucidated yet, novel functions of medications, including fenoldopam, theophylline and aminophylline, have been shown to have better outcomes for these patients. With the recent advances in identification of risk factors, outcomes, diagnosis, and management, the medical community can further explain the complexities of AKI in the pediatric population post-cardiac surgery.
| S-EPMC7530361 | biostudies-literature
Project description:BackgroundTo investigate the expression of ATF3 in the blood and urine of adult patients undergoing cardiopulmonary bypass (CPB) surgery and to identify the changes during the perioperative period of CPB, and to determine whether ATF3 can be used as a biological marker for the early diagnosis of acute kidney injury (AKI).MethodsWe prospectively studied 83 patients who underwent elective CPB (ECB). Relevant clinical information was collected. Blood and urine samples were collected preoperatively (T0) and at 2 h (T1), 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) after surgery, and grouped according to the occurrence of AKI. The changes in ATF3 levels were observed, and the accuracy of the diagnosis of AKI was compared through receiver operating characteristic (ROC) curve analysis. Factors influencing the expression of ATF3 at baseline were also analyzed.ResultsA total of 83 adult patients undergoing cardiac surgery with CPB were included, and 42 of them developed AKI. The levels of serum ATF3 (sATF3) in the AKI group were significantly higher than those in the non-AKI group 24 h after surgery, and the difference was statistically significant (662.62±204.72 vs. 586.93±175.87; P=0.0345). Urinary ATF3 (uATF3) increased significantly 6 h after surgery, and the area under the ROC curve (AUC) for diagnosing AKI 12 h after surgery was 0.691 (95% CI: 0.576-0.807). When uATF3 was higher than 1,216 pg/mL, the sensitivity and specificity for the diagnosis of AKI were 0.43 and 0.85, respectively. On the other hand, the preoperative expression of ATF3 was negatively correlated with the preoperative creatinine level, but not affected by the patient's age, weight, gender, preoperative cardiac function, preoperative blood routine examination and liver function.ConclusionsATF3 can be expressed early in the blood and urine of patients after CPB and can be used as a diagnostic marker for AKI after CPB in adult patients.
| S-EPMC8667156 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a frequent complication of cardiac surgery that poses significant risks for both the development of chronic kidney diseases and mortality. Our previous study illustrated that heightened expression levels of faecal and plasma indole metabolites before the operation were associated with ischemic AKI. In this study, we aimed to validate the supposition that plasma indole-3-aldehyde (I3A) could serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.MethodsThis statistical reanalysis utilized AKI metabolomic data from patients scheduled for cardiac surgery between April 2022 and July 2022 in two tertiary hospitals. Faecal and blood samples were prospectively collected before surgery within 24 h, and variables related to the preoperative, intraoperative, and postoperative periods were recorded. AKI diagnosis was based on the Kidney Disease Improving Global Outcomes criteria.ResultsIn this study, 55 patients who underwent cardiac surgery were analyzed, and 27 of them (49.1%) developed postoperative AKI. Before surgery, these patients had significantly higher levels of faecal indole metabolites, including skatole, trans-3-indoleacrylic acid, and 5-methoxyindoleacetic acid. The plasma I3A, clinical model that considered perioperative and intraoperative variables, and their combination had area under the receiver operating characteristic curve (ROC) values of 0.79 (95% CI 0.67-0.91), 0.78 (95% CI 0.66-0.90), and 0.84 (95% CI 0.74-0.94) for predicting AKI, respectively. Furthermore, by utilizing net reclassification improvement and integrated discrimination improvement, plasma I3A showed significant improvements in risk reclassification compared to the clinical model alone.ConclusionsThe dysregulation of gut microbiota metabolism in patients scheduled for cardiac surgery can result in an increase in indoles from tryptophan metabolism, which may be associated with postoperative acute kidney injury (AKI). This suggests that indoles may serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.
| S-EPMC10629179 | biostudies-literature
Project description:ObjectivesTo understand the effect of tight glycemic control on cardiac surgery-associated acute kidney injury.DesignSecondary analysis of data from the Safe Pediatric Euglycemia after Cardiac Surgery trial of tight glycemic control versus standard care.SettingPediatric cardiac ICUs at University of Michigan, C.S. Mott Children's Hospital, and Boston Children's Hospital.PatientsChildren 0-36 months old undergoing congenital cardiac surgery.InterventionsNone.Measurements and main resultsCardiac surgery-associated acute kidney injury was assigned using the Acute Kidney Injury Network criteria with the modification that a greater than 0.1 mg/dL increase in serum creatinine was required to assign cardiac surgery-associated acute kidney injury. We explored associations between cardiac surgery-associated acute kidney injury and tight glycemic control and clinical outcomes. Of 799 patients studied, cardiac surgery-associated acute kidney injury occurred in 289 patients (36%), most of whom had stage II or III disease (72%). Cardiac surgery-associated acute kidney injury rates were similar between treatment groups (36% vs 36%; p = 0.99). Multivariable modeling showed that patients with cardiac surgery-associated acute kidney injury were younger (p = 0.002), underwent more complex surgery (p = 0.005), and had longer cardiopulmonary bypass times (p = 0.002). Cardiac surgery-associated acute kidney injury was associated with longer mechanical ventilation and ICU and hospital stays and increased mortality. Patients at University of Michigan had higher rates of cardiac surgery-associated acute kidney injury compared with Boston Children's Hospital patients (66% vs 15%; p < 0.001), but University of Michigan patients with cardiac surgery-associated acute kidney injury had shorter time to extubation and ICU and hospital stays compared with Boston Children's Hospital patients.ConclusionsTight glycemic control did not reduce the cardiac surgery-associated acute kidney injury rate in this trial cohort. We observed significant differences in cardiac surgery-associated acute kidney injury rates between the two study sites, and there was a differential effect of cardiac surgery-associated acute kidney injury on clinical outcomes by site. These findings warrant further investigation to identify causal variation in perioperative practices that affect cardiac surgery-associated acute kidney injury epidemiology.
| S-EPMC5503840 | biostudies-literature
Project description:BackgroundChildren undergoing a cardiac surgical procedure are at increased risk for acute kidney injury (AKI). Novel biomarkers are needed to improve risk stratification of AKI after cardiac surgery.MethodsWe enrolled children aged 1 month to 18 years old from July 2007 to December 2010 undergoing cardiopulmonary bypass. Three United States Food and Drug Administration-approved plasma biomarkers of cardiac stretch, N-terminal pro B-type natriuretic peptide (NTproBNP), inflammation (ST2), or fibrosis (galectin-3), were measured preoperatively and postoperatively within 6 hours of cardiac surgery. All analyses were stratified by age (<2 or ≥2 years old) to account for changing biomarker distributions during childhood and due to a significant interaction between biomarker and age for galectin-3 and NTproBNP (P < .05).ResultsPostoperatively, AKI, defined by a doubling of baseline serum creatinine, was diagnosed in 51 of 194 children <2 years and in 28 of 201 children ≥2 years. After multivariable adjustment, for children <2 years, none of the biomarkers were independently associated with AKI, whereas for children ≥2 years, the highest tertile of preoperative galectin-3 and NTproBNP as well as the postoperative galectin-3 and ST2 were associated with AKI.ConclusionsPreoperative plasma galectin-3 and NTproBNP and the first postoperative galectin-3 and ST2 levels were independently associated with AKI in children ≥2 years old. The performance of cardiac biomarkers after cardiac surgical procedure is affected by age, and research is required to develop biomarkers for children <2 years old.
| S-EPMC7554084 | biostudies-literature
Project description:Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common postoperative complication following cardiac surgery. Currently, there are no reliable methods for the early prediction of CSA-AKI in hospitalized patients. This study developed and evaluated the diagnostic use of metabolomics-based biomarkers in patients with CSA-AKI. Methods and Results A total of 214 individuals (122 patients with acute kidney injury [AKI], 92 patients without AKI as controls) were enrolled in this study. Plasma samples were analyzed by liquid chromatography tandem mass spectrometry using untargeted and targeted metabolomic approaches. Time-dependent effects of selected metabolites were investigated in an AKI swine model. Multiple machine learning algorithms were used to identify plasma metabolites positively associated with CSA-AKI. Metabolomic analyses from plasma samples taken within 24 hours following cardiac surgery were useful for distinguishing patients with AKI from controls without AKI. Gluconic acid, fumaric acid, and pseudouridine were significantly upregulated in patients with AKI. A random forest model constructed with selected clinical parameters and metabolites exhibited excellent discriminative ability (area under curve, 0.939; 95% CI, 0.879-0.998). In the AKI swine model, plasma levels of the 3 discriminating metabolites increased in a time-dependent manner (R2, 0.480-0.945). Use of this AKI predictive model was then confirmed in the validation cohort (area under curve, 0.972; 95% CI, 0.947-0.996). The predictive model remained robust when tested in a subset of patients with early-stage AKI in the validation cohort (area under curve, 0.943; 95% CI, 0.883-1.000). Conclusions High-resolution metabolomics is sufficiently powerful for developing novel biomarkers. Plasma levels of 3 metabolites were useful for the early identification of CSA-AKI.
| S-EPMC8751958 | biostudies-literature
Project description:Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) may be related to the increase of chronic kidney disease and mortality in critically ill patients, so developing potential biomarkers is particularly important for disease prediction and early diagnosis. The purpose of this study was to investigate the alteration profiles of plasma metabolome and the possible links with urinary metabolome in patients with CSA-AKI. Methods: Non-targeted metabolomics was performed on plasma samples collected from groups of patients with CSA-AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney). The differential plasma metabolites associated with CSA-AKI were screened out using multivariate and univariate statistical methods, and altered metabolic pathways were identified by examining the Kyoto Encyclopedia of Genes and Genomes database. After receiver operating characteristic analysis to obtain potential biomarkers, the differential plasma metabolites with Level 1 were used for correlation analysis and metabolomic interplay with urinary metabolome. Results: Nearly 1750 plasma metabolites were identified through bioinformatics methods at Annotation Levels 1-3. The plasma metabolome of injured kidney can be well separated from the plasma metabolomes of uninjured or recovered groups, but the plasma samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using statistical analysis. Compared with the uninjured kidney group, the patients with CSA-AKI displayed dramatic changes in plasma metabolism, particularly for amino acid metabolism. As for the potential biomarkers with Level 1 identification in the plasma metabolome, carnitines and amino acid metabolites exhibited a significant positive correlation, while carnitines and organic acids in plasma also involved in the metabolomic interplay with urinary metabolome. Conclusions: Plasma metabolite disorder was observed in patients with CSA-AKI due to ischaemia and medical treatment, and the recovered patients’ systemic status were able to return to normal. This work provides data on plasma metabolite markers on CSA-AKI and possible link to urinary metabolome.
2024-12-29 | PXD059299 |