Kelly R McMahon1,2, Shahrad Rod Rassekh3, Kirk R Schultz3, Tom Blydt-Hansen4, Geoffrey D E Cuvelier5, Cherry Mammen4, Maury Pinsk6, Bruce C Carleton7, Ross T Tsuyuki8, Colin J D Ross9, Ana Palijan1, Louis Huynh10, Mariya Yordanova1, Frédérik Crépeau-Hubert1, Stella Wang11, Debbie Boyko8, Michael Zappitelli11,12,13. 1. Research Institute of the McGill University Health Centre, Montreal Children's Hospital, Division of Nephrology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada. 2. Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 3. British Columbia Children's Hospital, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada. 4. British Columbia Children's Hospital, Division of Pediatric Nephrology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada. 5. CancerCare Manitoba, Division of Pediatric Oncology-Hematology-BMT, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. 6. Section of Pediatric Nephrology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. 7. BC Children's Hospital Research Institute, Department of Pediatrics, Division of Translational Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada. 8. Epidemiology Coordinating and Research Centre, Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. 9. Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. 10. Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada. 11. Peter Gilgan Centre For Research and Learning, Toronto, Ontario, Canada. 12. Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. 13. Now with Toronto Hospital for Sick Children, Department of Pediatrics, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.
Abstract
Importance: Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective: To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants: This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Exposures: Cisplatin infusions. Main Outcomes and Measures: The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. Results: A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). Conclusions and Relevance: The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.
Importance: Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective: To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants: This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Exposures: Cisplatin infusions. Main Outcomes and Measures: The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. Results: A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). Conclusions and Relevance: The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.
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