Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study

Kelly R McMahon; Asaf Lebel; 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; Louis Huynh; Mariya Yordanova; Frédérik Crépeau-Hubert; Stella Wang; Ana Palijan; Jasmine Lee; Debbie Boyko; Michael Zappitelli; Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group

doi:10.1007/s00467-022-05745-5

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study

Pediatr Nephrol. 2023 May;38(5):1667-1685. doi: 10.1007/s00467-022-05745-5. Epub 2022 Oct 19.

Authors

Kelly R McMahon^{1

2}, Asaf Lebel^{3

4}, Shahrad Rod Rassekh⁵, Kirk R Schultz⁵, Tom D Blydt-Hansen⁶, Geoffrey D E Cuvelier⁷, Cherry Mammen⁶, Maury Pinsk⁸, Bruce C Carleton⁹, Ross T Tsuyuki¹⁰, Colin J D Ross¹¹, Louis Huynh¹², Mariya Yordanova¹³, Frédérik Crépeau-Hubert¹, Stella Wang¹⁴, Ana Palijan¹, Jasmine Lee¹⁴, Debbie Boyko¹⁰, Michael Zappitelli^{15

16

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

Affiliations

¹ Department of Pediatrics, Division of Nephrology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
² Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
³ Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Pediatric Nephrology Unit, Ha'Emek Medical Center, Afula, Israel.
⁵ Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia, British Columbia Children's Hospital, Vancouver, BC, Canada.
⁶ Department of Pediatrics, Division of Pediatric Nephrology, University of British Columbia, British Columbia Children's Hospital, Vancouver, BC, Canada.
⁷ Research Institute in Oncology and Hematology, CancerCare Manitoba, Department of Pediatrics and Child Health, Division of Pediatric Oncology-Hematology-BMT, University of Manitoba, Winnipeg, MB, Canada.
⁸ Department of Pediatrics and Child Health, Section of Pediatric Nephrology, University of Manitoba, Winnipeg, MB, Canada.
⁹ Department of Pediatrics, Division of Translational Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Epidemiology Coordinating and Research Centre, Departments of Pharmacology and Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
¹¹ Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
¹² Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.
¹³ Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹⁴ Child Health Evaluative Sciences, Peter Gilgan Centre For Research and Learning, Room 11th floor, 11.9722, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
¹⁵ Child Health Evaluative Sciences, Peter Gilgan Centre For Research and Learning, Room 11th floor, 11.9722, 686 Bay Street, Toronto, ON, M5G 0A4, Canada. michael.zappitelli@sickkids.ca.
¹⁶ Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. michael.zappitelli@sickkids.ca.
¹⁷ Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada. michael.zappitelli@sickkids.ca.

PMID: 36260162
DOI: 10.1007/s00467-022-05745-5

Abstract

Background: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes.

Methods: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines.

Results: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]).

Conclusions: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Acute kidney injury; Chronic kidney disease; Cisplatin nephrotoxicity; Epidemiology; Hypertension; Paediatric nephrology.

Publication types

Observational Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Acute Kidney Injury* / chemically induced
Acute Kidney Injury* / diagnosis
Acute Kidney Injury* / epidemiology
Canada
Child
Child, Preschool
Cisplatin / adverse effects
Electrolytes
Humans
Hypertension* / drug therapy
Kidney
Prospective Studies
Renal Insufficiency, Chronic* / complications
Retrospective Studies
Risk Factors

Substances

Cisplatin
Electrolytes

Grants and funding

CIHR/Canada