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PEDIATRICS Vol. 101 No. 6 June 1998, p. e8

ELECTRONIC ARTICLE:
Ifosfamide-induced Nephrotoxicity in Children: Critical Review of Predictive Risk Factors

Received Aug 19, 1997; accepted Jan 28, 1998.

Ronen Loebstein and Gideon Koren

From the Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Canada.

Ifosfamide is widely used in the treatment of pediatric solid tumors. Its main adverse effects are various forms of renal tubular and glomerular damage. Many risk factors have been proposed to play a role in the development and severity of nephrotoxicity in children receiving ifosfamide, among which are 1) patient's age, 2) cumulative ifosfamide dose, 3) concurrent administration of cis or carboplatinum, 4) unilateral nephrectomy, and 5) method of ifosfamide administration. However, presently there is no consensus regarding the weight of each one of them. Therefore, we critically reviewed the major studies that have evaluated the different risk factors in an attempt to determine the relative importance of each.

Cumulative ifosfamide doses of >= 60 g/m appears to be the most consistent independent predictor for both the development and the severity of nephrotoxicity, whereas a younger age (<5 years of age) was associated primarily with the more severe and chronic forms of proximal tubulopathy. Comparable incidence and severity forms of proximal tubulopathy among children who had been treated with cis platinum in addition to ifosfamide and those who had not indicate that platinums probably potentiate ifosfamide-induced renal damage rather than act as a major independent risk factor. Finally, although unilateral nephrectomy has been proposed as a significant risk factor in different studies, the relatively small number of nephrectomized children in these cohorts limit the strength of this association.

To reduce the frequency and severity of ifosfamide-induced nephrotoxicity, it appears that cumulative doses of 60 g/m should be considered carefully, especially in children <5 years of age.

Key words: ifosfamide, nephrotoxicity, proximal tubulopathy, risk factors, cumulative dose, age.


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