Kelly R McMahon1,2, Hayton Chui3,4, Shahrad Rod Rassekh5, Kirk R Schultz5, Tom D Blydt-Hansen6, Cherry Mammen6, Maury Pinsk7, Geoffrey D E Cuvelier8, Bruce C Carleton9, Ross T Tsuyuki10, Colin J D Ross11, Prasad Devarajan12, Louis Huynh13, Mariya Yordanova14, Frédérik Crépeau-Hubert1, Stella Wang3, Vedran Cockovski3, Ana Palijan1, Michael Zappitelli15,3. 1. Division of Nephrology, Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal Children's Hospital, Montreal, Quebec, Canada. 2. Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 3. Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada. 4. Faculty of Health Sciences, McMaster Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada. 5. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 6. Division of Pediatric Nephrology, Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 7. Department of Pediatrics and Child Health, Section of Pediatric Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada. 8. Division of Pediatric Oncology-Hematology-BMT, Department of Pediatrics and Child Health, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada. 9. Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia and BC Children's Hospital and Research Institute, Vancouver, British Columbia, Canada. 10. EPICORE Centre, Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. 11. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 12. Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. 13. Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada. 14. Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, Quebec, Canada. 15. Department of Pediatrics, Division of Nephrology, Toronto Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Abstract
Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.
Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.
Authors: Shveta S Motwani; Gearoid M McMahon; Benjamin D Humphreys; Ann H Partridge; Sushrut S Waikar; Gary C Curhan Journal: J Clin Oncol Date: 2018-01-10 Impact factor: 44.544
Authors: Chirag R Parikh; Heather Thiessen-Philbrook; Amit X Garg; Deepak Kadiyala; Michael G Shlipak; Jay L Koyner; Charles L Edelstein; Prasad Devarajan; Uptal D Patel; Michael Zappitelli; Catherine D Krawczeski; Cary S Passik; Steven G Coca Journal: Clin J Am Soc Nephrol Date: 2013-04-18 Impact factor: 8.237
Authors: Michael Bennett; Catherine L Dent; Qing Ma; Sudha Dastrala; Frank Grenier; Ryan Workman; Hina Syed; Salman Ali; Jonathan Barasch; Prasad Devarajan Journal: Clin J Am Soc Nephrol Date: 2008-03-12 Impact factor: 8.237
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