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.

Clinical Utility of Biomarkers of AKI in Cardiac Surgery and Critical Illness

“…Similar to the adult cohort, urine IL-18 and urine and plasma NGAL levels in the pediatric patients peaked within 6 hours of ICU arrival, significantly preceding serum creatinine (24-48 hours postoperative) (19). In the pediatric cohort, the first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI, defined by receipt of dialysis or doubling in serum creatinine during hospital stay.…”

“…The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with AUCs of 0.72 and 0.71, respectively. In this pediatric cohort, none of the quintiles of plasma NGAL were independently associated with the development of postoperative severe AKI (19 (22).…”

“…Many of these previously published studies are limited in that they are small single-center studies with low severe AKI event rates (10)(11)(12)(13)(14)(15)(16)(17). However, within the last year, data from the first large international, prospective observational study investigating biomarkers after cardiac surgery have been published (18)(19)(20)(21)(22). The Translational Research Investigating Biomarker Endpoints in AKI (TRIBE AKI) study assembled a cohort of 1219 adults undergoing coronary artery bypass grafting and/or valvular surgery cardiac surgery and 311 children undergoing surgery for congenital cardiac lesions.…”

“…In the near future, we anticipate that these investigations will include a combination of clinical risk factors and multiple biomarkers to predict the clinical course and prognosis. To date, several investigations have sought to combine AKI biomarkers with clinical information to determine if the addition of the novel marker improves risk stratification (18,19,27,(36)(37)(38). Few studies have incorporated preexisting standardized clinical models/scores (e.g., Acute Physiology, Age, Chronic Health Evaluation [APACHE] or Mehta Score for cardiac surgery) (47), because most of these risk stratification scores were constructed and validated to detect end points other than nondialysis-requiring AKI (26).…”

Are we ready for the clinical use of novel acute kidney injury biomarkers?

“…In neonates, SCr-based AKI definitions are additionally complicated because at birth SCr reflects maternal creatinine, which improves over the first few weeks of life, dependent on gestational age [9]. For these and other reasons, newer definitions of a neonatal AKI using noninvasive serum and urine biomarkers are greatly needed.Studies in VLBW infants [10,11], infants who undergo cardiopulmonary bypass surgery [3,[12][13][14][15][16][17], and other sick newborns admitted to a neonatal intensive care unit [18] suggest that such biomarkers can detect those infants who will later have a rise in SCr and that they may also predict hard clinical endpoints, such as mortality. However, there are several challenges in validating urine AKI biomarkers.…”