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26-06-2023 | Acute Kidney Injury | Original Article

Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin

Authors: Hayton Chui, Kelly R. McMahon, Shahrad Rod Rassekh, Kirk R. Schultz, Tom D. Blydt-Hansen, Cherry Mammen, Maury Pinsk, Geoffrey D. E. Cuvelier, Bruce C. Carleton, Ross T. Tsuyuki, Colin J. D. Ross, Prasad Devarajan, Louis Huynh, Mariya Yordanova, Frédérik Crépeau-Hubert, Stella Wang, Vedran Cockovski, Ana Palijan, Michael Zappitelli, for the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group

Published in: Pediatric Nephrology | Issue 1/2024

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Abstract

Background

Cisplatin is associated with acute kidney injury (AKI) and electrolyte abnormalities. Urine tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) may be early cisplatin-AKI biomarkers.

Methods

We conducted a 12-site prospective cohort study with pediatric patients treated with cisplatin (May 2013–December 2017). Blood and urine (measured for TIMP-2, IGFBP-7) were collected pre-cisplatin, 24-h post-cisplatin, and near hospital discharge during the first or second cisplatin cycle (early visit (EV)) and during second-to-last or last cisplatin cycle (late visit (LV)). Primary outcome: serum creatinine (SCr)-defined AKI (≥ stage 1).

Results

At EV (median (interquartile (IQR)) age: 6 (2–12) years; 78 (50%) female), 46/156 (29%) developed AKI; at LV, 22/127 (17%) experienced AKI. At EV, TIMP-2, IGFBP-7, and TIMP-2*IGFBP-7 pre-cisplatin infusion concentrations were significantly higher in participants with vs. those without AKI. At EV and LV, biomarker concentrations were significantly lower in participants with vs. those without AKI at post-infusion and near-hospital discharge. Biomarker values normalized to urine creatinine were higher in patients with AKI compared to without (LV post-infusion, median (IQR): TIMP-2*IGFBP-7: 0.28 (0.08–0.56) vs. 0.04 (0.02–0.12) (ng/mg creatinine)2/1000; P < .001). At EV, pre-infusion biomarker concentrations had the highest area under the curves (AUC) (range: 0.61–0.62) for AKI diagnosis; at LV, biomarkers measured post-infusion and near discharge yielded the highest AUCs (range: 0.64–0.70).

Conclusions

TIMP-2*IGFBP-7 were poor to modest at detecting AKI post-cisplatin. Additional studies are needed to determine whether raw biomarker values or biomarker values normalized to urinary creatinine are more strongly associated with patient outcomes.

Graphical abstract

Appendix
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Metadata
Title
Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin
Authors
Hayton Chui
Kelly R. McMahon
Shahrad Rod Rassekh
Kirk R. Schultz
Tom D. Blydt-Hansen
Cherry Mammen
Maury Pinsk
Geoffrey D. E. Cuvelier
Bruce C. Carleton
Ross T. Tsuyuki
Colin J. D. Ross
Prasad Devarajan
Louis Huynh
Mariya Yordanova
Frédérik Crépeau-Hubert
Stella Wang
Vedran Cockovski
Ana Palijan
Michael Zappitelli
for the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group
Publication date
26-06-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2024
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-023-06007-8

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