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The influence of age on nephrotoxicity following chemotherapy in children
R Skinner1, A D Pearson, L Price
1Department of Child Health, Medical School, University of Newcastle upon Tyne, UK.
Insights
Pediatric patients under 5 treated with ifosfamide experienced more severe proximal tubular damage than older children. Cisplatin showed no age-related renal function differences, but ifosfamide toxicity in young children may impact growth.
Area of Science:
- Pediatric Nephrology
- Oncology
- Pharmacology
Background:
- Chemotherapy agents like ifosfamide and cisplatin can cause nephrotoxicity in children.
- Age-related differences in renal function and toxicity susceptibility are not well-established for these agents.
Purpose of the Study:
- To compare renal function and nephrotoxicity between younger (≤5 years) and older (>5 years) children treated with ifosfamide or cisplatin.
- To identify potential age-specific risks of chemotherapy-induced kidney damage.
Main Methods:
- Assessed glomerular filtration rate (GFR) using 51chromium-labelled edetic acid clearance.
- Evaluated proximal tubular function via plasma/urine electrolytes, glucose, fractional excretions, and beta-2 microglobulin.
- Assessed distal tubular function using morning urine osmolality.
Main Results:
- Younger children receiving ifosfamide exhibited significantly more proximal tubular toxicity (lower plasma phosphate, higher glucose fractional excretion) than older children.
- No significant differences in glomerular or distal tubular function were observed with ifosfamide based on age.
- Cisplatin treatment did not reveal any age-related differences in glomerular, proximal, or distal tubular function.
Conclusions:
- Ifosfamide-induced proximal tubular toxicity is more pronounced in younger children, potentially affecting long-term growth and development.
- Cisplatin appears to have a similar safety profile regarding renal function across different pediatric age groups.
- Age stratification is crucial when assessing chemotherapy-related nephrotoxicity, particularly for ifosfamide.
Abstract:
Nephrotoxicity is an important adverse effect of chemotherapy in children. Renal function after treatment with either ifosfamide or cisplatinum in children aged 5 years or less ('younger children') was compared with that in those over 5 years ('older children'). Eighteen children (six younger, 12 older) given ifosfamide were studied after completion of chemotherapy, and 28 patients (16 younger, 12 older) were evaluated after cisplatinum. Glomerular filtration rate was measured from the plasma clearance of 51chromium-labelled edetic acid. Proximal tubular function was assessed by determination of plasma and urine calcium, phosphate, magnesium and glucose concentration; calculations of their fractional excretions, and of the renal threshold for phosphate; and measurement of urinary excretion of beta 2-microglobulin. Distal tubular function was evaluated by measurement of the early morning urine osmolality. Younger children had more severe proximal tubular toxicity than older children treated with ifosfamide, with significantly lower plasma phosphate concentrations and higher fractional excretions of glucose. However, there was no evidence of any such difference in glomerular or distal tubular damage after ifosfamide, and no difference in any aspect of renal function between younger and older children treated with cisplatinum. Increased proximal tubular toxicity after ifosfamide in younger children may have serious implications for future growth and development.