title: Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study.
abstract: Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight.We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r=-0.527, P=<0.001).
authors: From the Departamento de Nefrología, Hospital Infantil de México Federico Gómez (CAJ-T); Unidad de Investigación en Epidemiología Clínica, Hospital Infantil de México Federico Gómez (ODC-M, PC); Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social (RR-R); Facultad de Medicina de la Universidad Nacional Autónoma de México, México D.F., México (RR-R, PC); Pharmaceutical Outcomes Programme, BC Children's Hospital (RJ-M, BC); Division of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia (BC, RJ-M); Child&Family Research Institute, Vancouver, Canada (RJ-M, BC); Departamento de Oncología, Hospital Infantil de México Federico Gómez, México D.F., México (AM); Department of Oncology, BC Children's Hospital Vancouver, Canada (RR); Departamento de Farmacología, CINVESTAV IPN (GC-H); Laboratorio de Investigación en Nefrología y Metabolismo Mineral, Hospital Infantil de México Federico Gómez (MM); and Departamento de Farmacología, Facultad de Medicina UNAM, México D.F., México (MM).
authors: Clímaco Andres
authors: CA
authors: Jiménez-Triana
authors: Osvaldo D
authors: OD
authors: Castelán-Martínez
authors: Rodolfo
authors: R
authors: Rivas-Ruiz
authors: Ricardo
authors: R
authors: Jiménez-Méndez
authors: Aurora
authors: A
authors: Medina
authors: Patricia
authors: P
authors: Clark
authors: Rod
authors: R
authors: Rassekh
authors: Gilberto
authors: G
authors: Castañeda-Hernández
authors: Bruce
authors: B
authors: Carleton
authors: Mara
authors: M
authors: Medeiros
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006128:Growth / Q000187:drug effects*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D015995:Prevalence; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin