Renal function in children and adolescents following 72 g/m2 of ifosfamide

Abstract

A detailed analysis of the renal function of 18 children and adolescents aged 7-20 years (median, 16 years) was performed at least 3 months following the completion of a non-platinum-containing chemotherapy regimen with a total dose of 72 g/m2 of ifosfamide. Ifosfamide had been given as a 1-h infusion of 1.8 g/m2 daily for 5 days at 5- to 6-week intervals along with mesna uroprotection. The mean glomerular filtration rate (GFR) as determined by inulin clearance was 100 ml/min/1.73 m2. Although 6 of 18 patients had GFRs below normal, the lowest was only 18% less than the lower limit of normal and would not account for any clinical compromise. The renal plasma flow and filtration fraction were normal. Proximal tubular function evaluation revealed normal fractional excretion (FE) of glucose; normal mean tubular maximum phosphate reabsorption per GFR (TMP)/GFR values; high FE of urate (17%); and mild, generalized aminoaciduria in 6 of the 18 patients. Distal tubular function evaluation showed normal 24-h urinary calcium levels and FE of magnesium as well as normal urinary osmolality after water deprivation. Two patients had mild proteinuria. The findings in this study are encouraging in terms of the lack of clinically significant renal abnormalities observed in patients who had received a cumulative dose of 72 g/m2 of ifosfamide.

Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma

“…We have previously reported a detailed analysis of renal function in patients following a cumulative dose of 72 g/m 2 ifosfamide without CDDP [22]. The renal function in that group of patients was similar to the group described here with a planned cumulative dose of 54 g/m 2 ifosfamide and 360 mg/m 2 CDDP.…”

Progressive glomerular toxicity of ifosfamide in children

“…They showed evidence of subclinical glomerular impairment by SDS-PAGE urine protein electrophoresis [29], 6 and 7 months after the end of therapy. Median follow-up in previous studies [26,27] was considerably less than ours and this may be a reason for their lower incidence.…”

“…The first report of persistent and significant glomerular impairment in children in 1988 [25] was followed by two others [5,14] over the next few years. An incidence of glomerular impairment in 17.1% following I F 0 is higher than previous reports of 0-9.9% [4,13,[26][27][28]. Inclusion of every IFO-treated patient since the computerization of biochemical data storage and chronological exclusion of 22 patients from any analysis were intended to provide accuracy of assessment.…”

True

“…Although early studies failed to reveal any evidence of nephrotoxicity in children receiving ifosfamide (de Kraker and Voute, 1984;Gasparini, 1986;Biron et al, 1987;Kellie et al, 1988;Demeocq et al, 1989), subsequent reports described a characteristic pattern of proximal renal tubular damage, often accompanied by glomerular and sometimes by distal tubular impairment (Smeitink et al, 1988;Burk et al, 1990;Skinner et al, 1990;Pratt et al, 1991;Suarez et al, 1991;Caron et al, 1992;Shore et al, 1992;De Schepper et al, 1993;Arndt et al, 1994;Ashraf et al, 1994). Such toxicity persisted long after discontinuation of ifosfamide treatment in many patients, often presenting with clinical manifestations due to the Fanconi syndrome (Skinner et al, 1993).…”