title: Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study.
abstract: BACKGROUND
  Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited.
  
  
  OBJECTIVE
  To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension).
  
  
  METHODS
  This is a 3-year observational prospective cohort study.
  
  
  METHODS
  The study includes 12 Canadian pediatric oncology centers.
  
  
  METHODS
  The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin.Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2or a pre-existing renal transplantation at baseline.
  
  
  METHODS
  Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected.
  
  
  METHODS
  Outcomes:AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines.Procedure:Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes).
  
  
  CONCLUSIONS
  The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved.
  
  
  CONCLUSIONS
  ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: McMahon
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Shahrad
authors.initials: S
authors.lastname: Rod Rassekh
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
authors.affiliation: Department of Pediatrics and Child Health, CancerCare Manitoba, University of Manitoba, Winnipeg, Canada.
authors.forename: Maury
authors.initials: M
authors.lastname: Pinsk
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Blydt-Hansen
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Cherry
authors.initials: C
authors.lastname: Mammen
authors.affiliation: Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Ross T
authors.initials: RT
authors.lastname: Tsuyuki
authors.affiliation: Division of Nephrology & Hypertension, Cincinnati Children's Hospital Medical Center, OH, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Department of Pediatrics and Child Health, CancerCare Manitoba, University of Manitoba, Winnipeg, Canada.
authors.forename: Geoff D E
authors.initials: GD
authors.lastname: Cuvelier
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Stollery Children's Hospital, University of Alberta, Edmonton, Canada.
authors.forename: Lesley G
authors.initials: LG
authors.lastname: Mitchell
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baruchel
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Palijan
authors.affiliation: Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Colin J D
authors.initials: CJ
authors.lastname: Ross
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Zappitelli
keywords: acute kidney injury; cisplatin nephrotoxicity; cohort study; pediatrics; urinary biomarkers