Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury. Issue 1 (27th January 2022)

• Record Type: Journal Article
• Authors: McMahon, Kelly R.; Chui, Hayton; Rassekh, Shahrad Rod; Schultz, Kirk R.; Blydt-Hansen, Tom D.; Mammen, Cherry; Pinsk, Maury; Cuvelier, Geoffrey D. E.; Carleton, Bruce C.; Tsuyuki, Ross T.; Ross, Colin J.D.; Devarajan, Prasad; Huynh, Louis; Yordanova, Mariya; Crépeau-Hubert, Frédérik; Wang, Stella; Cockovski, Vedran; Palijan, Ana; Zappitelli, Michael
• Is Part Of: Kidney360. Volume 3:Issue 1(2022)
• Page Start: 37
• Page End: 50
• Publication Date: 2022-01-27
• Subjects: acute kidney injury and ICU nephrology -- acute kidney injury -- chemotherapy -- cisplatin nephrotoxicity -- cohort studies -- diagnostic testing -- kidney injury molecule-1 -- neutrophil gelatinase-associated lipocalin -- pediatric hematology/oncology -- pediatric nephrology -- urine biomarkers; 616.61
• DOI: 10.34067/KID.0004802021
• Languages: English
• ISSNs: 2641-7650

Abstract

Key Points: Urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were high in patients with AKI. Clinical usefulness and associations with late kidney outcomes should be evaluated. Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI in children. There is a need to identify other tubular injury biomarkers in children treated with cisplatin. Visual Abstract: Abstract : Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with 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, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (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 the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0–232.7] versus 14.9 [5.4–29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083–9077] versus 1049 [358–3326] pg/mg creatinine; P <0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56–0.72; KIM-1, 0.48–0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54–0.75) versus early infusions (AUC-ROC range, 0.48–0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.