Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery.
ABSTRACT 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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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.The Journal of Physiology 06/2014; 592(18). DOI:10.1113/jphysiol.2014.273078 · 4.54 Impact Factor
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ABSTRACT: L’insuffisance rénale aiguë (IRA) est le terme générique utilisé pour décrire une diminution rapide du débit de filtration glomérulaire (DFG), ainsi que ses conséquences sur les déchets azotés. Les définitions actuelles de l’IRA tiennent compte de la diurèse et de l’élévation de la créatinine plasmatique. Si l’oligurie ou l’anurie peuvent survenir rapidement, elles témoignent aussi bien d’une adaptation rénale à une hypovolémie que de la présence de lésions ischémiques sévères. La créatinine plasmatique est un marqueur des variations du DFG qui n’est ni sensible ni spécifique. Son élévation est, de plus, tardive après agression rénale. Afin de diagnostiquer plus précocement l’IRA, de détecter l’agression rénale ou l’existence de lésions tubulaires, plusieurs marqueurs fonctionnels ou lésionnels ont été développés. Les dosages plasmatique ou urinaire de NGAL (neutrophil gelatinase-associated lipocalin) ou de la cystatine C, le dosage urinaire de KIM-1 (kidney injury molecule-1) ou de la NHE3 (sodium-hydrogene exchanger type 3) sont autant de biomarqueurs proposés, prometteurs dans les études préliminaires, mais dont les études de confirmation tardent à venir. Dans cette revue, nous préciserons les limites aux définitions actuelles de la créatinine plasmatique, les résultats actuels obtenus avec ces nouveaux biomarqueurs et les principales limites à leur utilisation ou à l’interprétation des données disponibles à ce jour.Réanimation 07/2012; 21(4). DOI:10.1007/s13546-012-0487-4
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ABSTRACT: Over the last decade, therapy for lupus nephritis in children has begun to shift from the provision of long-term steroids and intravenous cyclophosphamide to regimens with limited or no cyclophosphamide, lower steroid burdens, and increased reliance on oral mycophenolate mofetil. As the molecular immunology underlying the pathophysiology of lupus is further discerned, more targeted therapies, including the use of monoclonal antibodies against immune cells or cell signaling factors, may come to play a larger role in the treatment of pediatric lupus. Similarly, as experience with autologous stem cell transplantation for therapy-resistant disease is gained in adults, its potential applicability to such situations in children may be clarified. Over the next few decades, children with lupus will benefit as well from the identification of new biomarkers that are both sensitive and specific to disease activity, allowing clinicians to more readily assess response to therapy and diagnose disease flare.03/2012; 1(1). DOI:10.1007/s40124-012-0005-1