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Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy
Author(s) -
Sterling Maya,
AlIsmaili Zubaida,
McMahon Kelly R.,
Piccioni Melissa,
Pizzi Michael,
Mottes Theresa,
Lands Larry C.,
Abish Sharon,
Fleming Adam J.,
Bennett Michael R.,
Palijan Ana,
Devarajan Prasad,
Goldstein Stuart L.,
O'Brien Maureen M.,
Zappitelli Michael
Publication year - 2017
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26538
Subject(s) - medicine , acute kidney injury , nephrotoxicity , kidney disease , urine , biomarker , creatinine , urology , carboplatin , ifosfamide , lipocalin , chemotherapy , gastroenterology , kidney , cisplatin , biochemistry , chemistry
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.