Comparison of Urinary Biomarkers for Early Detection of Acute Kidney Injury After Cardiopulmonary Bypass Surgery in Infants and Young Children

Abstract

Acute kidney injury (AKI) is a potential complication for children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery. This study was designed to investigate and compare the predictive values of urinary biomarkers for AKI after CPB surgery in infants and young children and to determine the optimal timing of testing and the cutoff value for each biomarker. The study prospectively enrolled 58 CHD children 3 years of age or younger who were undergoing CPB surgery. Urinary neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), microalbumin (MA), N-acetyl-ß-D-glucosaminidase (NAG), α1-microglobulin (α1-MG), and creatinine (UCr) were measured at baseline and at various time points after surgery. Children who experienced AKI had more complex cardiac surgical procedures as evaluated by Risk Adjustment for Congenital Heart Surgery 1 (RACHS-1), longer CPB and aortic clamping times, and worse clinical outcomes than those who did not. In the AKI group, all five urinary biomarkers increased substantially and peaked at 4 h after surgery. In contrast, in the non-AKI group, they increased slightly or had no significant changes during the first 24 h. All the biomarkers had the best predictive performances at 4 h after surgery. At this time point, NAG had the minimum area under the curve (AUC) (0.747), which was significantly lower than that of the others (AUC, 0.82-0.85; P < 0.05). The optimal cutoff value of each biomarker was 290 ng/mg UCr for NAGL, 1,477 pg/mg UCr for IL-18, 400 mg/g UCr for MA, 225 U/g UCr for NAG, and 290 mg/g UCr for α1-MG. In conclusion, urinary NGAL, IL-18, MA, and α1-MG had similar predictive performances for the early detection of AKI after CPB surgery in infants and young children.

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…Overall, only a few clinical studies have examined the use of IL-18 as an AKI biomarker [53]. These investigations showed reasonable results in pediatric patients with AKI after cardiac surgery [31,129]. Nevertheless, other studies failed to indicate strong predictive ability of IL-18 for AKI among the ICU or emergency department population [20,32].…”

Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

“…This was in line with some previous studies. 6,7,12,18,20 However, CPb duration was significantly longer in the AKI group than in the non-AKI group(P=0.033). In agreement with this finding,boldt et al observed that post-operative levels of NGAL were related to the duration of CPb.…”

“…Hence, pediatric subjects are the ideal population in which to investigate AKI after cardiac surgery. 20 The exclusion criteria in our study were preexisting renal insufficiency or the use of nephrotoxic drugs. We studied a homogeneous population of children with possibly no major confounding variables, in whom the only obvious renal insult would be the result of an ischemia-reperfusion injury after cardiac surgery.…”

“…Many studies have supported the hypothesis that duration bears a negative impact on postoperative renal function. 2,[5][6][7]18,19,20,22,23 Sethi et al reported that duration of CPB >90 minutes could cause AKI in adults. 24 Similarly, Zheng et al reported that AKI was significantly more common in patients with duration of CPB >90 minutes.…”

“…24 Similarly, Zheng et al reported that AKI was significantly more common in patients with duration of CPB >90 minutes. 20 Although the mechanism is unknown, the release of proinflammatory mediators, coagulation products, oxidation products, and the adhesion of blood cells to the vascular endothelium reportedly increases with prolonged CPb time. 25 We found no significant difference between the AKI and non-AKI groups in cross-clamp duration (P=0.344).…”