Hemojuvelin Predicts Acute Kidney Injury and Poor Outcomes Following Cardiac Surgery.
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ABSTRACT:
SUBMITTER: Ko SW
PROVIDER: S-EPMC5792584 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
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Hemojuvelin Predicts Acute Kidney Injury and Poor Outcomes Following Cardiac Surgery.
Ko Sheng-Wen SW Chi Nai-Hsin NH Chi Nai-Hsin NH Wu Che-Hsiung CH Huang Tao-Min TM Chueh Shih-Chieh Jeff SJ Wang Chih-Hsien CH Lin Jui-Hsiang JH Wang Wei-Jie WJ Ting Jui-Tsung JT Chang Huang-Ming HM Connolly Rory R Lai Chien-Heng CH Tseng Li-Jung LJ Wu Vin-Cent VC Chu Tzong-Shinn TS
Scientific reports 20180131 1
Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristi ...[more]
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Project description:Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.
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Project description:Background Alterations in serum creatinine levels delay the identification of severe cardiac surgery-associated acute kidney injury. To provide timely diagnosis, novel predictive tools should be investigated. Methods and Results This prospective observational study consists of a screening cohort (n=204) and a validation cohort (n=198) from 2 centers from our hospital. Thirty-two inflammatory cytokines were measured via a multiplex cytokine assay. Least absolute shrinkage and selection operator regression was conducted to select the cytokine signatures of severe cardiac surgery-associated acute kidney injury. Afterwards, the significant candidates including interferon-γ, interleukin-16, and MIP-1α (macrophage inflammatory protein-1 alpha) were integrated into the logistic regression model to construct a predictive model. The predictive accuracy of the model was evaluated in these 2 cohorts. The cytokine-based model yielded decent performance in both the screening (C-statistic: 0.87, Brier 0.10) and validation cohorts (C-statistic: 0.86, Brier 0.11). Decision curve analysis revealed that the cytokine-based model had a superior net benefit over both the clinical factor-based model and the established plasma biomarker-based model for predicting severe acute kidney injury. In addition, elevated concentrations of each cytokine were associated with longer mechanical ventilation times, intensive care unit stays, and hospital stays. They strongly predicted the risk of composite events (defined as treatment with renal replacement therapy and/or in-hospital death) (OR of the fourth versus the first quartile [95% CI]: interferon-γ, 27.78 [3.61-213.84], interleukin-16, 38.07 [4.98-291.07], and MIP-1α, 9.13 [2.84-29.33]). Conclusions Our study developed and validated a promising blood cytokine-based model for predicting severe acute kidney injury after cardiac surgery and identified prognostic biomarkers for assisting in outcome risk stratification.
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Project description:Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.
| S-EPMC4931708 | biostudies-literature
Project description:Background:Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post-cardiac surgery AKI. Methods:Single-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)-Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4. Results:A total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m2, and estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, the combination of peak serum cystatin C and peak urine KIM-1/creatinine (Cr) (6 hours post-CPB to POD 1) above optimal cutoff significantly associated with postoperative AKI (odds ratio [OR]: 5.32; 95% confidence interval [CI]: 1.31-21.67; P = 0.020). This biomarker combination significantly improved the performance of the clinical model for the prediction of postoperative AKI (area under the curve [AUC]: 0.77, 95% CI: 0.65-0.90 for the clinical model alone versus 0.83, 95% CI: 0.73-0.93 for the clinical model with the addition of biomarker data, P = 0.049). Conclusions:Combining biomarkers of postoperative kidney function loss and postoperative kidney tubular damage significantly improved prediction of in-hospital AKI following cardiac surgery. Future large, multicenter studies are warranted to assess whether panels of biomarkers reflecting distinct pathobiology can be used to guide interventions and improve short- and long-term outcomes in patients undergoing cardiac surgery.
| S-EPMC6698294 | biostudies-literature