Tubular Injury Biomarkers to Predict Chronic Kidney Disease and Hypertension at 3-Months Post-Cisplatin in Children

Ryan S Huang; Kelly R McMahon; Stella Wang; Hayton Chui; Asaf Lebel; Jasmine Lee; Vedran Cockovski; Shahrad Rod Rassekh; Kirk R Schultz; Tom D Blydt-Hansen; Geoffrey D E Cuvelier; Cherry Mammen; Maury Pinsk; Bruce C Carleton; Ross T Tsuyuki; Colin J D Ross; Ana Palijan; Michael Zappitelli; Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group*

doi:10.34067/KID.0000000000000448

Tubular Injury Biomarkers to Predict Chronic Kidney Disease and Hypertension at 3-Months Post-Cisplatin in Children

Kidney360. 2024 Apr 26. doi: 10.34067/KID.0000000000000448. Online ahead of print.

Authors

Ryan S Huang^{1

2}, Kelly R McMahon³, Stella Wang², Hayton Chui^{2

4}, Asaf Lebel², Jasmine Lee², Vedran Cockovski², Shahrad Rod Rassekh⁵, Kirk R Schultz⁵, Tom D Blydt-Hansen⁶, Geoffrey D E Cuvelier⁷, Cherry Mammen⁵, Maury Pinsk⁸, Bruce C Carleton⁹, Ross T Tsuyuki¹⁰, Colin J D Ross¹¹, Ana Palijan³, Michael Zappitelli^{1

2}; Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group*

Affiliations

¹ Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
² Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
³ Department of Pediatrics, Division of Nephrology, Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
⁴ Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.
⁵ Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
⁶ Department of Pediatrics, Division of Pediatric Nephrology, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
⁷ Department of Pediatric Hematology-Oncology-BMT, CancerCare Manitoba, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Pediatrics and Child Health, Section of Pediatric Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada.
⁹ Department of Pediatrics, Division of Translational Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁰ EPICORE Centre, Departments of Pharmacology and Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
¹¹ Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

PMID: 38668904
DOI: 10.34067/KID.0000000000000448

Abstract

Background: Urine kidney injury biomarkers measured during cisplatin therapy may identify patients at risk for adverse subsequent kidney outcomes. We examined relationships between tubular injury biomarkers collected early (early visit [EV]: first or second cisplatin cycle) and late (late visit [LV]: last or second-last cisplatin cycle) during cisplatin therapy, with 3-month post-cisplatin chronic kidney disease (CKD) and hypertension.

Methods: We analyzed data from the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment Nephrotoxicity Study: twelve-center prospective cohort study of 159 children receiving cisplatin. We measured urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine, kidney injury molecule-1 (KIM-1)/creatinine, tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP-7) (TIMP-2 and IGFBP-7 expressed as their product, ng/ml^2/1000) at an EV and LV during cisplatin therapy with pre-infusion, post-infusion, and hospital discharge sampling. Area under the curve (AUC) was calculated for biomarkers to detect 3-month post-cisplatin CKD (KDIGO guidelines: low estimated glomerular filtration rate (eGFR) or elevated uACR for age) and hypertension (three blood pressures; per American Academy of Pediatrics guidelines).

Results: At median follow-up of 90 days, 52/118 (44%) and 17/125 (14%) developed CKD and hypertension, respectively. Biomarker prediction for 3-month CKD was low to modest; NGAL combined with KIM-1 at EV discharge yielded the highest AUC (0.67, 95% CI 0.57-0.77). Biomarker prediction of 3-month hypertension was stronger, but modest; the highest AUC was from combining EV pre-infusion NGAL and TIMP-2*IGFBP-7 (0.71, 95% CI 0.62-0.80). When EV pre-infusion NGAL and TIMP-2*IGFBP-7 were added to the 3-month hypertension clinical predictive model, AUCs increased from 0.81 (0.72-0.91) to 0.89 (0.83-0.95) (p<0.05).

Conclusions: Tubular injury biomarkers we studied were individually not strong predictors of 3-month post-cisplatin kidney outcomes. Adding biomarkers to existing clinical prediction models may help predict post-therapy hypertension and identify higher kidney-risk patients.

Abstract

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