Group analysis identifies differentially elevated biomarkers with distinct outcomes for advanced acute kidney injury in cardiac surgery.
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ABSTRACT:
SUBMITTER: Lin H
PROVIDER: S-EPMC5753615 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Group analysis identifies differentially elevated biomarkers with distinct outcomes for advanced acute kidney injury in cardiac surgery.
Lin Haiqun H Scherzer Rebecca R Philbrook Heather Thiessen HT Coca Steven G SG Wilson Francis Perry FP Garg Amit X AX Shlipak Michael G MG Parikh Chirag R CR
Biomarkers in medicine 20171127 12
<h4>Aim</h4>To investigate early postoperative biomarkers for risk discrimination of advanced acute kidney injury (AKI).<h4>Materials & methods</h4>Postoperative plasma biomarkers including NGAL, h-FABP, CK-MB, hsTNT, NT-proBNP, IL-6, IL-10 and VEGF were analyzed using group-based method among 426 patients with AKI after cardiac surgery.<h4>Results</h4>Six patient groups with distinct biomarker patterns were identified. Individual biomarker displayed significant difference across the groups. The ...[more]
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Project description:BackgroundAcute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI.MethodsIn this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge.ResultsPatients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p < 0.001).ConclusionsWhen added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.
| S-EPMC5921971 | biostudies-literature
Project description:Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.
| S-EPMC3338298 | 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
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:Acute kidney injury (AKI) is a common and severe complication after cardiac surgery. Currently, a series of novel biomarkers have favored the assessment of AKI after cardiac surgery in addition to the conventional indicators. The biomartkers, such as urinary liver fatty acid binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), serum L-FABP, heart-type FABP, kidney injury molecule 1 (KIM-1), and interleukin-18 were found to be significantly higher in patients who developed AKI after cardiac surgery than those who did not. Apart from urinary interleukin-18, the novel biomarkers have been recognized as reliable indicators for predicting the diagnosis, adverse outcome, and even mortality of AKI after cardiac surgery. The timing of the renal replacement therapy is a significant predictor relating to patients' prognoses. In patients with AKI after cardiac surgery, renal replacement therapy should be performed as early as possible in order to achieve promising outcomes. In children, AKI after cardiac surgery can be managed with peritoneal dialysis. AKI after cardiac surgery has received extensive attention as it may increase early mortality and impact long-term survival of patients as well. The purpose of this article was to analyze the changes of the pertinent biomarkers, to explore the related risk factors leading to the occurrence of AKI after cardiac surgery, and to provide a basis for the clinical prevention and reduction of AKI.
| S-EPMC6629228 | biostudies-literature
Project description:BACKGROUND:We previously reported that children undergoing cardiac surgery are at high risk for long-term chronic kidney disease (CKD) and hypertension, although postoperative acute kidney injury (AKI) is not a risk factor for worse long-term kidney outcomes. We report here our evaluation of renal injury biomarkers 5 years after cardiac surgery to determine whether they are associated with postoperative AKI or long-term CKD and hypertension. METHODS:Children aged 1 month to 18 years old undergoing cardiopulmonary bypass were recruited to this prospective cohort study. At 5 years after cardiac surgery, we measured urine interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, YKL-40, and neutrophil gelatinase-associated lipocalin (NGAL). Biomarker levels were compared between patients with AKI and those without. We also performed a cross-sectional analysis of the association between these biomarkers with CKD and hypertension. RESULTS:Of the 305 subjects who survived hospitalization, four (1.3%) died after discharge, and 110 (36%) participated in the 5-year follow-up. Of these 110 patients, 49 (45%) had AKI. Patients with versus those without postoperative AKI did not have significantly different biomarker concentrations at 5 years after cardiac surgery. None of the biomarker concentrations were associated with CKD or hypertension at 5 years of follow-up, although CKD and hypertension were associated with a higher proportion of participants with abnormal NGAL levels. CONCLUSIONS:Postoperative pediatric AKI is not associated with urinary kidney injury biomarkers 5 years after surgery. This may represent a lack of chronic renal injury after AKI, imprecise estimation of the glomerular filtration rate, the need for longer follow-up to detect chronic renal damage, or that our studied biomarkers are inadequate for evaluating subclinical chronic renal injury.
| S-EPMC5945328 | biostudies-literature
Project description:Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.
| S-EPMC5698070 | biostudies-literature
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.
| S-EPMC3171944 | biostudies-literature
Project description:Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery 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 patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery.
| S-EPMC3171945 | biostudies-literature
Project description:Background:Acute kidney injury (AKI) following cardiac surgery leads to increased morbidity and mortality. Characterization and validation of early biomarkers of AKI may ultimately facilitate early therapeutic intervention. We have previously identified that elevated urinary hepcidin-25 is inversely and independently associated with the development of AKI in adult cardiac surgery patients. Hepcidin-25 is an antimicrobial peptide that sequesters iron intracellularly, and its elevation following human ischemia reperfusion injury may represent a renoprotective response to minimize renal injury. Objective:Our goal was to validate urinary hepcidin-25 as a non-invasive biomarker in an independent cardiac surgery cohort, within the context of clinical AKI predictors. Design:Prospective observational cohort study. Setting:Adult cardiac surgery program at St. Boniface Hospital, Winnipeg, Manitoba, Canada. Patients:Adult cardiac surgery patients undergoing cardiopulmonary bypass (CPB), n = 306. Measurements:Urine hepcidin-25, measured on post-operative day (POD) 1. Methods:A prospective, observational cohort of adult CPB patients (n = 306) was collected with serial perioperative urine samples. Urine hepcidin-25 at POD 1 was measured by competitive ELISA. Its diagnostic performance was evaluated in conjunction with clinical parameters and the Thakar clinical prediction score, using multivariate logistic regression. Results:Urinary hepcidin-25 is elevated following cardiac surgery in AKI and non-AKI patients. Elevated urinary hepcidin-25 concentration was inversely associated with AKI on both univariate (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.83, P = .002) and multivariate analysis (OR: 0.67, 95% CI: 0.50-0.95, P = .02). A combined model with clinical risk factors demonstrated that baseline estimated glomerular filtration rate (eGFR), diabetes mellitus, and urinary hepcidin-25 concentration had an overall area under the curve (AUC) of 0.82 (0.75-0.88) for predicting subsequent AKI development, which was superior to clinical prediction alone as determined by the Thakar score. Limitations:(1) A single-center observational study. (2) Polyclonal antibody-based competitive ELISA. Conclusion:Hepcidin-25 is inversely associated with AKI in a multivariate model when combined with eGFR and diabetes mellitus, with an overall AUC of 0.82. Notably, urinary hepcidin-25 improves on clinical AKI prediction compared to the Thakar score alone.
| S-EPMC5788097 | biostudies-literature