Urine Biomarkers of Acute Kidney Injury in Noncritically Ill, Hospitalized Children Treated with Chemotherapy

Overview

Journal Pediatr Blood Cancer

Specialties Hematology
Oncology
Pediatrics

Date 2017 Apr 19

PMID 28417544

Citations 11

Authors

Maya Sterling

Zubaida Al-Ismaili

Kelly R McMahon

Melissa Piccioni

Michael Pizzi

Theresa Mottes

Larry C Lands

Sharon Abish

Adam J Fleming

Michael R Bennett

Ana Palijan

Prasad Devarajan

Stuart L Goldstein

Maureen M OBrien

Michael Zappitelli

Affiliations

Soon will be listed here.

Abstract

Background: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis.

Procedure: We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition. We compared postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3 days later) to pre-infusion concentrations. We calculated area under the receiver operating characteristic curve (AUC) for postinfusion biomarkers to discriminate for AKI.

Results: Prechemotherapy infusion NGAL and IL-18 concentrations were not higher than nonchemotherapy control concentrations. Increasing chemotherapy dose was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P < 0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were significantly higher than pre-infusion biomarker concentrations (P < 0.05), during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all biomarker AUCs (Cis-Carb and Ifos) improved.

Conclusion: Urine NGAL and IL-18 show promise as early AKI diagnostic tests in children treated with ifosfamide and may have a potential role in drug toxicity monitoring.

Citing Articles

Clinical questions and good practice statements of clinical practice guidelines for management of kidney injury during anticancer drug therapy 2022.

Yanagita M, Muto S, Nishiyama H, Ando Y, Hirata S, Doi K Clin Exp Nephrol. 2023; 28(2):85-122.

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Advances in the study of subclinical AKI biomarkers.

Zou C, Wang C, Lu L Front Physiol. 2022; 13:960059.

PMID: 36091391 PMC: 9449362. DOI: 10.3389/fphys.2022.960059.

Kidney Damage and Stress Biomarkers for Early Identification of Drug-Induced Kidney Injury: A Systematic Review.

Desai R, Kazarov C, Wong A, Kane-Gill S Drug Saf. 2022; 45(8):839-852.

PMID: 35831683 DOI: 10.1007/s40264-022-01202-2.

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

McMahon K, Chui H, Rassekh S, Schultz K, Blydt-Hansen T, Mammen C Kidney360. 2022; 3(1):37-50.

PMID: 35368557 PMC: 8967607. DOI: 10.34067/KID.0004802021.

Urine NGAL and KIM-1-Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study.

Latoch E, Kononczuk K, Muszynska-Roslan K, Taranta-Janusz K, Wasilewska A, Szymczak E J Clin Med. 2021; 10(3).

PMID: 33494327 PMC: 7866176. DOI: 10.3390/jcm10030399.

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