Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Pediatric Cardiac Surgery

Section of Nephrology, Yale University and VAMC, 950 Campbell Avenue, Mail Code 151B, West Haven, CT 06516, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 08/2011; 22(9):1737-47. DOI: 10.1681/ASN.2010111163
Source: PubMed


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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    • "Some clinical models were evaluated for the purpose of AKI prediction after cardiac surgery [20]. Because there were little data for estimating such a clinical model in Korean population, we adopted the clinical model from Parikh et al. [21] with some modifications. Their clinical models included common variables in other AKI models, such as age, sex, race, CPB time, nonelective surgery, preoperative eGFR, diabetes, and hypertension. "
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    ABSTRACT: Objectives: Development of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is relatively common and associated with increased mortality. Recently, plasma neutrophil gelatinase-associated lipocalin (NGAL) was used for the prediction of AKI. We evaluated the clinical usefulness of plasma NGAL. Design and methods: One hundred twelve adult patients undergoing cardiovascular surgery with CPB were included. Blood samples were obtained at baseline, at intensive care unit (ICU) admission, and 24h after ICU admission. The development of AKI, which is defined as an increase in serum creatinine by more than 50% within 3 postoperative days, was monitored. NGAL levels were analyzed by a Biosite Triage meter (Alere Medical, USA). Diagnostic performance of NGAL was analyzed using the area under the receiver operating characteristic curve. Results: In AKI patients (n=13), plasma NGAL levels at ICU admission were significantly higher than those at baseline [177 (122-402) vs. 121 (74-158) ng/mL, median (interquartile range), p=0.028], whereas serum creatinine showed no significant change. The predictive value of NGAL at ICU admission was 0.812 [95% confidence interval (CI), 0.68 to 0.95] with a cut-off value of 168.5ng/mL (sensitivity, 61.5%; specificity, 88.9%). After the exclusion of 35 patients with preoperative decreased renal function, the predictive value was increased to 0.911 (95% CI, 0.82 to 1.00). Conclusions: This study showed that plasma NGAL may serve as a useful biomarker for the early detection of AKI in adult patients following CPB.
    Full-text · Article · Oct 2014 · Clinical Biochemistry
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    • "Increasing acceptance of standardized definitions of AKI amongst nephrologists and intensivists has advanced several aspects of AKI research yet the practical issue of what constitutes “true AKI” clinically, remains unsettled [3-8]. Novel biomarkers have demonstrated promising associations with AKI [3,4], leading to a resurgence in clinical trials in the setting of AKI [9]. However, given the suboptimal performance of some biomarkers, there is only limited data to support the role of accurate adjudication of AKI to improve the diagnostic and discriminative performance of traditional and modern markers of renal function [10]. "
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    ABSTRACT: Adjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)). We enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers. There was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss’ Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours. The etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results. Trial registration NCT00774137
    Full-text · Article · Jul 2014 · BMC Nephrology
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    • "NGAL is particularly advantageous in pediatric cardiac surgery patients for highly accurate prediction of AKI. Urinary NGAL performs better than serum NGAL in most studies (Mishra et al. 2005; Koyner et al. 2008; Tuladhar et al. 2009; Parikh et al. 2011b), but this observation is less pronounced (Parikh et al. 2011a) or even reversed (Koyner et al. 2012) "
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    ABSTRACT: Cardiovascular disease (CVD) and kidney disease are closely interrelated. Disease of one organ can induce dysfunction of the other, ultimately leading to failure of both. Clinical awareness of synergistic adverse clinical outcomes in patients with coexisting CVD and kidney disease or 'cardiorenal syndrome (CRS)' has existed. Renal dysfunction, even mild, is a strong independent predictor for adverse clinical outcomes in CVD patients. Developing therapeutic interventions targeting acute kidney injury (AKI) has been limited due mainly to lack of effective tools to accurately detect AKI in a timely manner. Neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 have been recently demonstrated to be potential candidate biomarkers in patients undergoing cardiac surgery. However, further validating AKI biomarkers is needed especially in the setting of acute decompensated heart failure and acute myocardial infarction where AKI commonly occurs. The other concern with regard to understanding the pathogenesis of renal complications in CVD is that mechanistically-oriented study has been relatively rare. Pre-clininal studies have shown that activation of renal inflammation-fibrosis processes, likely triggered by hemodynamic derangement, underlies CVD-associated renal dysfunction. On the other hand, it is postulated that there still are likely missing links in the heart-kidney connection in CRS patients with significant renal dysfunction. At present, nondialyzable protein-bound uremic toxins (PBUTs) appear to be the main focus in this regard. Evidence of the causal role of PBUTs in CRS has been increasingly demonstrated, mainly focusing on indoxyl sulfate (IS) and p-cresyl sulfate (pCS). Both IS and pCS are derived from colonic microbiotic metabolism of dietary amino acids, hence the colon has become a target of treatment in addition to efforts in improving dialysis techniques for better removal of PBUTs. Novel therapy targeting site of toxin production has led to new prospects in early intervention for predialysis patients with chronic kidney disease. This article is protected by copyright. All rights reserved.
    Preview · Article · Jun 2014 · The Journal of Physiology
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