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Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery.

ABSTRACT: Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery.This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3].Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23%) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6-4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6-2.2 pg/mL) (p?=?0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16-35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p?=?0.0001).Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.

SUBMITTER: Greenberg JH

PROVIDER: S-EPMC4537680 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery.

Greenberg Jason H JH Whitlock Richard R Zhang William R WR Thiessen-Philbrook Heather R HR Zappitelli Michael M Devarajan Prasad P Eikelboom John J Kavsak Peter A PA Devereaux P J PJ Shortt Colleen C Garg Amit X AX Parikh Chirag R CR

Pediatric nephrology (Berlin, Germany) 20150415 9

<h4>Background</h4>Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery.<h4>Methods</h4>This is a sub-study of the Translational Research Investigating ...[more]

PMID: 25877915

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Project description:BackgroundCardiac 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.MethodsSingle-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.ResultsA 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).ConclusionsCombining 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.

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.

Dataset Information

Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery.

Publications

Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery.

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