Long-term evaluation of ifosfamide-related nephrotoxicity in children: The French experience

Abstract

9551 Background: Ifosfamide-induced nephrotoxicity is a significant issue in patients treated for tumours during childhood. This study aimed at documenting incidence of late renal toxicity of ifosfamide and its risk factors. Methods: 183 patients have been investigated. 100 were male. Median age at treatment was 9.3 years (0.4–18 years). Median dose of ifosfamide was 54 g/m2 (18–77 g/m2). No patients received cisplatin and/or carboplatinum. Diagnoses included rhabdomyosarcoma (77), other soft tissue sarcoma (39), Ewing (39), and osteosarcoma (28). Investigations were performed at a median interval of 10.3 years (5–20.7) after the end of the treatment, at a median age of 21.6 years (7.1–44.2). No patient had electrolyte or vitamine supplementation. Glomerular and tubular functions were graded according to the Skinner's system. Results: After 5 year minimal follow-up 55% had normal tubular and 79% had normal glomerular functions. Natraemia, kalaemia, serum HCO3 and calcaemia were normal in all patients. Hypomagnesaemia was observed in 4, hypophosphaetemia in 8 %. The tubular threshold for phosphate was reduced in 44% of the patients (grade 2 or 3 in 15%, grade 3 in 1 pt). Significant glycosuria (> 0.5 g/24h) was detected in 5 % of the patients but it was clearly abnormal only in 5 patients. 34% of the patients had beta2 microglobulinuria, however, proteinuria was observed in only 12%. Cumulative dose of ifosfamide, older age at treatment and follow-up since treatment were predictor for tubulopathy in univariate and multivariate analyse. The glomerular filtration rate was normal in 79% of the patients. 21% had a grade 1 toxicity and 1 patient a grade 2. Univariate analysis did not find any prognostic factor for glomerular toxicity apart from the association with tubular toxicity. Conclusions: Since ifosfamide-induced renal toxicity can be severe, long term evaluation is important and this risk should be balanced carefully against efficacy. No significant financial relationships to disclose.