Kelly R McMahon1,2, Asaf Lebel3,4, 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 Zappitelli15,16,17. 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.
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.
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.
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Authors: Kelly R McMahon; Shahrad Rod Rassekh; Kirk R Schultz; Tom Blydt-Hansen; Geoffrey D E Cuvelier; Cherry Mammen; Maury Pinsk; Bruce C Carleton; Ross T Tsuyuki; Colin J D Ross; Ana Palijan; Louis Huynh; Mariya Yordanova; Frédérik Crépeau-Hubert; Stella Wang; Debbie Boyko; Michael Zappitelli Journal: JAMA Netw Open Date: 2020-05-01