A novel use for novel acute kidney injury biomarkers: fenoldopam's effect on neutrophil gelatinase-associated lipocalin and cystatin C

The past decade of clinical and translational acute kidney injury (AKI) research has focused on the validation of novel biomarkers to detect AKI earlier, to ultimately provide researchers and clinicians with a much sought-after golden window of opportunity to prevent AKI development or mitigate its course. In the current study, Ricci and colleagues take the next logical step to use two novel biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, in a novel manner to define AKI rather than predict AKI [1]. In their randomized trial, the investigators demonstrate the α1-selective dopamine agonist fenoldopam to be associated with lower post-operative urinary NGAL and cystatin C concentrations compared with placebo. Furthermore, fenoldopam-treated children had a lower rate of reaching a urinary NGAL threshold of 200 ng/ml, suggesting its renoprotective effects, despite no differences in creatinine-associated AKI development by the pediatric RIFLE criteria [2].Children undergoing bypass represent an ideal model for AKI biomarker study since the timing of the kidney injury is known, interventions can be planned ahead of time, and children do not have many of the co-morbidities of adulthood that can complicate studies [3,4]. Previous trials of fenoldopam in children and adults to prevent serum-creatinine-defined AKI have had mixed results [5-8], with pediatric observational studies showing a benefit in terms of enhanced urine output postoperatively. The chronological paradigm shift evaluating intraoperative agent administration to detect its effect on an early and sensitive marker of AKI such as NGAL provides a model for future randomized trials in this field.Importantly, the recent pooled analysis of 10 pediatric and adult studies by Haase and colleagues showing that 'NGAL-positive, serum creatinine-negative AKI' was associated with equivalent or worse outcomes compared with 'creatinine-positive, NGAL-negative AKI' [9] provides strong support for Ri