Ifosfamide-induced nephrotoxicity in children: critical review of predictive risk factors

Area of Science:

• Pediatric Oncology
• Nephrology
• Clinical Pharmacology

Background:

• Ifosfamide is a crucial chemotherapy agent for pediatric solid tumors.
• Ifosfamide treatment can lead to significant renal toxicity, affecting both tubules and glomeruli.
• Several factors are implicated in ifosfamide-induced nephrotoxicity, but their relative importance is unclear.

Purpose of the Study:

• To critically review existing studies on risk factors for ifosfamide nephrotoxicity in children.
• To determine the relative importance of various risk factors, including age, dose, and co-administered drugs.
• To provide evidence-based recommendations for minimizing renal damage during ifosfamide therapy.

Main Methods:

• Systematic review of major studies evaluating risk factors for ifosfamide nephrotoxicity.
• Analysis of patient age, cumulative ifosfamide dose, concurrent platinum-based chemotherapy, prior nephrectomy, and administration method.
• Comparative assessment of the impact of each factor on nephrotoxicity development and severity.

Main Results:

• Cumulative ifosfamide doses of ≥60 g/m are the most consistent independent predictor of nephrotoxicity.
• Younger age (<5 years) is associated with more severe and chronic proximal tubulopathy.
• Concurrent cisplatin or carboplatin administration may potentiate renal damage but are not major independent risk factors; unilateral nephrectomy's role is limited by small cohort sizes.

Conclusions:

• Cumulative ifosfamide dose is the most critical factor in predicting and preventing nephrotoxicity.
• Careful consideration of cumulative doses (≥60 g/m) is essential, particularly in young children (<5 years).
• Further research is needed to fully elucidate the impact of factors like unilateral nephrectomy.