IFOSFAMIDE-INDUCED NEPHROTOXICITY IN CHILDREN - CRITICAL-REVIEW OF PREDICTIVE RISK-FACTORS

Ifosfamide is widely used in the treatment of pediatric solid tumors. its main adverse effects are various forms of renal tubular and glomer ular damage. Many risk factors have been proposed to play a role in th e development and severity of nephrotoxicity in children receiving ifo sfamid, among which are 1) patient's age, 2) cumulative ifosfamide dos e, 3) concurrent administration of cia or carboplatinum, 4) unilateral nephrectomy, and 5) method of ifosfamide administration. However, pre sently there is no consensus regarding the weight of each one of them. Therefore, we critically reviewed the major studies that have evaluat ed the different risk factors in an attempt to determine the relative importance of each. Cumulative ifosfamide doses of greater than or equ al to 60 g/m(2) appears to be the most consistent independent predicto r for both the development and the severity of nephrotoxicity, whereas a younger age (<5 years of age) was associated primarily with the mor e severe and chronic forms of proximal tubulopathy. Comparable inciden ce and severity forms of proximal tubulopathy among children who had b een 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. Fina lly, although unilateral nephrectomy has been proposed as a significan t risk factor in different studies, the relatively small number of nep hrectomized children in these cohorts limit the strength of this assoc iation. To reduce the frequency and severity of ifosfamide-induced nep hrotoxicity, it appears that cumulative doses of 60 g/m(2) should be c onsidered carefully, especially in children <5 years of age.