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Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study
Clímaco Andres Jiménez-Triana1, Osvaldo D Castelán-Martínez, Rodolfo Rivas-Ruiz
1From 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).
Insights
Cisplatin treatment in children can cause significant kidney damage (nephrotoxicity) and impair growth. Even mild nephrotoxicity (Grade 1) increases the risk of poor height development in pediatric cancer patients.
Area of Science:
- Pediatric Oncology
- Nephrology
- Clinical Pharmacology
Background:
- Cisplatin is a vital chemotherapy agent for solid tumors.
- Cisplatin is recognized for its nephrotoxic potential.
- Pediatric cancer patients receiving cisplatin are at risk for kidney damage and growth impairment.
Purpose of the Study:
- To determine the prevalence and severity of cisplatin-induced nephrotoxicity in children.
- To investigate the impact of cisplatin nephrotoxicity on longitudinal growth (height and weight).
Main Methods:
- Retrospective cohort study of 54 children treated with cisplatin.
- Monitoring of serum creatinine, electrolytes, height, and weight throughout cisplatin cycles and for 12 months post-treatment.
- Grading of nephrotoxicity from 0 to 4 based on serum creatinine levels and electrolyte disturbances.
Main Results:
- Nephrotoxicity occurred in 75.9% of patients, with Grade 1 (33.3%) and Grade 3 (33.3%) being most common.
- Younger patients and those receiving higher cisplatin doses experienced more severe nephrotoxicity.
- Nephrotoxicity was associated with impaired longitudinal growth, particularly a worsening of height Z-score at 12 months.
- Grade 1 nephrotoxicity significantly increased the risk of impaired growth (OR 5.1).
- Higher cisplatin doses correlated with lower serum magnesium levels at 12 months.
Conclusions:
- Cisplatin-induced nephrotoxicity is highly prevalent in pediatric patients.
- Cisplatin nephrotoxicity negatively impacts growth, with even mild cases posing a risk.
- Close monitoring of renal function and growth is crucial for children undergoing cisplatin therapy.
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).
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