Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury

Background: Few studies have described associations between acute kidney injury (AKI) biomarkers, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), and AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin based on Kidney Disease: Improving Global Outcomes guidelines criteria (≥stage 1). Results: Of 159 children, 156 (median [interquartile (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty-six of 156 (29%) and 22/127 (17%) developed AKI within 10 days of cisplatin administration following early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with vs. without AKI (near hospital discharge of late cisplatin infusion, median [IQR]: NGAL: 76.1 [10.0-232.7] vs. 14.9 [5.4-29.7] ng/mg creatinine; KIM-1: 4415 [2083-9077] vs. 1049 [358-3326] pg/mg creatinine; P