Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass.
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ABSTRACT: Background and objectives
Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.Design, setting, participants, & measurements
A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively.Results
Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P < 0.0005). Increased log(10) hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log(10) hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.Conclusions
Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.
SUBMITTER: Ho J
PROVIDER: S-EPMC3359550 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThe study objectives were to describe the incidence, risk factors, and outcomes of acute kidney injury after cardiopulmonary bypass in Jamaica.MethodWe performed a review of the medical records of adult patients (aged ≥ 18 years) with no prior dialysis requirement undergoing cardiopulmonary bypass at the University Hospital of the West Indies, Mona, between January 1, 2016, and June 30, 2019. Demographic, preoperative, intraoperative, and postoperative data were abstracted. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes criteria. The primary outcomes were acute kidney injury incidence and all-cause 30-day mortality. Multivariable logistic regression and Cox proportional analyses were used to examine the association between the acute kidney injury risk factors and the primary outcome.ResultsData for 210 patients (58% men, mean age 58.1 ± 12.9 years) were analyzed. Acute kidney injury occurred in 80 patients (38.1%), 44% with Kidney Disease Improving Global Outcomes I, 33% with Kidney Disease Improving Global Outcomes II, and 24% with Kidney Disease Improving Global Outcomes III. From multivariable logistic regression models, European System for Cardiac Operative Risk Evaluation II (odds ratio, 1.19; 95% confidence interval, 1.01-1.39 per unit), bypass time (odds ratio, 1.94; 95% confidence interval, 1.40-2.67 per hour), perioperative red cell transfusion (odds ratio, 3.03; 95% confidence interval, 1.36-6.76), and postoperative neutrophil lymphocyte ratio (odds ratio, 1.65; 95% confidence interval, 1.01-2.68 per 10-unit difference) were positively associated with acute kidney injury. Acute kidney injury resulted in greater median hospital stay (18 vs 11 days, P < .001) and intensive care unit stay (5 vs 3 days, P < .001), and an 8-fold increase in 30-day mortality (hazard ratio, 8.15; 95% confidence interval, 2.76-24.06, P < .001).ConclusionsAcute kidney injury after cardiopulmonary bypass surgery occurs frequently in Jamaica and results in poor short-term outcomes. Further studies coupled with quality interventions to reduce the mortality of those with acute kidney injury are needed in the Caribbean.
| S-EPMC9510884 | biostudies-literature
Project description:BackgroundAcute 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.ObjectiveOur 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.DesignProspective observational cohort study.SettingAdult cardiac surgery program at St. Boniface Hospital, Winnipeg, Manitoba, Canada.PatientsAdult cardiac surgery patients undergoing cardiopulmonary bypass (CPB), n = 306.MeasurementsUrine hepcidin-25, measured on post-operative day (POD) 1.MethodsA 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.ResultsUrinary 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.ConclusionHepcidin-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
Project description:Recent studies have recognized several risk factors for cardiopulmonary bypass- (CPB-) associated acute kidney injury (AKI). However, the lack of early biomarkers for AKI prevents practitioners from intervening in a timely manner. We reviewed the literature with the aim of improving our understanding of the risk factors for CPB-associated AKI, which may increase our ability to prevent or improve this condition. Some novel early biomarkers for AKI have been introduced. In particular, a combinational use of these biomarkers would be helpful to improve clinical outcomes. Furthermore, we discuss several interventions that are aimed at managing CPB-associated AKI, may increase the effect of renal replacement therapy (RRT), and may contribute to preventing CPB-associated AKI. Collectively, the conclusions of this paper are limited by the availability of clinical trial evidence and conflicting definitions of AKI. A guideline is urgently needed for CPB-associated AKI.
| S-EPMC7963912 | biostudies-literature
Project description:We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI).Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes.Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a ?50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement.AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction.Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.
| S-EPMC3220882 | biostudies-literature
Project description:IntroductionConventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker.MethodsWe studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay.ResultsIn AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease.ConclusionsOur findings suggest that urine hepcidin is an early predictive biomarker of ruling out AKI after CPB, thereby contributing to early patient risk stratification.
| S-EPMC3387629 | biostudies-literature
Project description:BACKGROUND:Several novel biomarkers that predict acute kidney injury (AKI) have recently been proposed. We have evaluated the sequential patterns of biomarker elevation after pediatric cardiopulmonary bypass (CPB) and determined their diagnostic accuracy. METHODS:We measured the ability of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7), to predict AKI (?50% increase in serum creatinine from baseline). Areas under the receiver-operator characteristic curves (AUCs) were calculated for each biomarker and for various biomarker combinations at multiple time points after CPB. RESULTS:Of 150 patients examined, AKI had developed in 50 patients by 24 h after CPB, with an elevated NGAL concentration first noted at 2 h post-CPB, increases in IL-18, L-FABP, and the product of TIMP-2 and IGFBP7 first noted at 6 h, and an elevated KIM-1 level noted at 12 h. At each time point, urine NGAL remained the marker with the highest predictive ability (AUC > 0.9). The addition of any other biomarker did not increase the predictive accuracy of NGAL alone at 2 and 6 h. At 12 h, when compared to NGAL alone, the combination of NGAL, IL-18, and TIMP2 improved the AUC for AKI prediction (from 0.938 to 0.973). CONCLUSIONS:While urine NGAL remains a superior stand-alone test at the 2 and 6 h time points after pediatric CPB, a panel of carefully selected biomarkers may prove optimal at later time points.
| S-EPMC7441589 | biostudies-literature
Project description:BackgroundAcute kidney injury after cardiac surgery is common and associated with increased mortality. It is unknown whether an intended higher arterial pressure during cardiopulmonary bypass reduces the incidence of acute and chronic kidney injury.MethodsPatients were randomised either to a control group or a high pressure group (arterial pressure > 60 mmHg). The inclusion criteria were age > 70 years, combined cardiac surgery and serum creatinine < 200 μmol/L. Glomerular filtration rate using the Cr-EDTA clearance method was measured the day before surgery and 4 months postoperatively. The RIFLE criteria were used to define the presence of acute kidney injury. In addition, the ratio between urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and creatinine was measured.ResultsNinety patients were included. Mean age was 76 ± 4 years and 76% were male. Mean arterial pressure was 47 ± 5 mmHg in the control group and 61 ± 4 mmHg in the high pressure group (p < 0.0001). The change in glomerular filtration rate at follow-up was - 9 ± 12 ml/min in the control group and - 5 ± 16 ml/min in the high pressure group (p = 0.288, 95% CI - 13 to 4). According to the RIFLE criteria 38% in the control group and 46% in the high pressure group developed acute kidney injury (p = 0.447). The postoperative urinary NGAL/creatinine ratio was comparable between the groups.ConclusionsAn intended increase in arterial pressure during cardiopulmonary bypass to > 60 mmHg did not decrease the incidence of acute or chronic kidney injury after cardiac surgery.Trial registrationClinicaltrials.gov, identifier: NCT01408420 . Registered 3rd of August 2011.
| S-EPMC6567467 | biostudies-literature
Project description:Acute kidney Injury (AKI) following open-heart surgery with cardiopulmonary bypass (CPB) is associated with an increased morbidity and mortality. The goal of this study is to explore patterns of gene expression in human AKI following CPB. This prospective observational study was approved by the Institutional Review Board Human Subjects Committee. Design and methods: Peripheral blood RNA samples were collected prospectively from a cohort of 30 patients at Caritas St. Elizabeths Medical Center in Boston, MA, undergoing CPB at time points immediately prior, and two and 24 hours following CPB. Gene expression patterns of four patients who developed AKI (cases) following CPB will be compared with six patients matched for clinical characteristics, who did not develop AKI (controls). AKI was defined by an incremental increase in serum creatinine of 30% within 72 hours following CPB. For peripheral blood RNA sampling, 2.5 ml of venous whole blood was collected into PAXgene Blood RNA Tube collection tubes (PreAnalytiX GmbH, Hombrechtikon, CH). Whole blood RNA was extracted with the PAXgene Blood RNA extraction Kit according to the manufacturers instructions (PAXgene RNA Kit Handbook, 06/2005). All biological samples are stored at 80° C.
2009-12-12 | E-TABM-595 | biostudies-arrayexpress
Project description:Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary ? and ? glutathione S-transferases (?-GST and ?-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. ?-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative ?-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative ?-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.
| S-EPMC4544762 | biostudies-literature
Project description:BackgroundAcute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort.MethodsThis was a retrospective analysis of patients under 1 year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk.ResultsWe included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve = 0.66, 95% CI = 0.60 - 0.72, sensitivity = 56.1%, specificity = 69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve = 0.65, 95% CI = 0.58 - 0.72, sensitivity = 52.6%, specificity = 74.6%).ConclusionIndexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.
| S-EPMC10487348 | biostudies-literature