Progressive renal toxicity due to ifosfamide

Heney, David; Wheeldon, J.; Rushworth, Parker; Chapman, Carleton B.; Lewis, Ian; Bailey, Chris

doi:10.1007/bf00878375

Cited by 12 publications

(23 citation statements)

References 2 publications

(2 reference statements)

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“…The argument for later onset and progressive nature is further strengthened by the fact that two of the children with clinical glomerular impairment were part of our previously published report [8]. They showed evidence of subclinical glomerular impairment by SDS-PAGE urine protein electrophoresis [29], 6 and 7 months after the end of therapy.…”

mentioning

confidence: 89%

“…Long-term clinically significant glomerular insufficiency, due to IFO, is not as well recognized. We have previously reported subclinical biochemical abnormalities of glomerular function in patients being followed as part of a prospective study of I F 0 tubular dysfunction [8]. Our attention was focused on the potential problem of clinical glomerular toxicity when we recently treated a patient who developed abnormal glomerular function during IF0 therapy and subsequently progressed to renal failure.…”

Section: Introductionmentioning

confidence: 99%

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Progressive glomerular toxicity of ifosfamide in children

Prasad

Lewis

Aparicio

et al. 1996

Med. Pediatr. Oncol.

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confidence: 89%

Section: Introductionmentioning

confidence: 99%

Progressive glomerular toxicity of ifosfamide in children

Prasad

Lewis

Aparicio

et al. 1996

Med. Pediatr. Oncol.

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“…Considerably larger numbers of patients would need to be entered into a study to have sufficient power to confirm a statistically significant difference between the schedules, however the similarity of the changes after the CI and the SI suggest that clinically important differences are unlikely. It is known that ifosfamide causes cumulative damage (Heney et al, 1991;Caron et al, 1992;Al Sheyyab et al, 1993) which could confound the results, however the cumulative dose before each schedule was very similar and no treatment-period interaction was demonstrated, although again the numbers are small.…”

Section: Discussionmentioning

confidence: 88%

“…There is evidence that renal damage occurs early on in treatment with ifosfamide and is progressive (Heney et al, 1991;Caron et al, 1992;Al Sheyyab et al, 1993), but acute changes in renal function following one course of treatment have not yet been related to long-term renal damage. This study compares the nephrotoxicity of different schedules of ifosfamide in the same patients.…”

Section: Discussionmentioning

confidence: 99%

“…Acute changes in renal function were compared in 16 children receiving 9 g m-2 of ifosfamide as a 72-h continuous infusion on one occasion and, on another course, divided into three 1 -h infusions on consecutive days. Subclinical acute nephrotoxicity was demonstrated with both schedules, but there were no significant differences in severity.Keywords: ifosfamide; nephrotoxicity; ifosfamide administration Subclinical renal damage has been reported in most children treated with ifosfamide (Skinner et al, 1990;Heney et al, 1991), and in some series between 20% and 40% of children have required some form of mineral replacement therapy because of inappropriate renal tubular loss of phosphate and bicarbonate (Skinner et al, 1990;Caron et al, 1992;De Schepper et al, 1993). Renal failure may occur acutely and prevent the delivery of planned chemotherapy, however it is more often a chronic problem with severely affected children suffering from hypophosphataemic rickets, renal tubular acidosis and occasionally nephrogenic diabetes insipidus.…”

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confidence: 99%

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The influence of ifosfamide scheduling on acute nephrotoxicity in children

English

Skinner²,

Pearson³

et al. 1997

Br J Cancer

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Summary Nephrotoxicity is a significant problem in children after treatment with ifosfamide. Acute changes in renal function were compared in 16 children receiving 9 g m-2 of ifosfamide as a 72-h continuous infusion on one occasion and, on another course, divided into three 1 -h infusions on consecutive days. Subclinical acute nephrotoxicity was demonstrated with both schedules, but there were no significant differences in severity.Keywords: ifosfamide; nephrotoxicity; ifosfamide administration Subclinical renal damage has been reported in most children treated with ifosfamide (Skinner et al, 1990;Heney et al, 1991), and in some series between 20% and 40% of children have required some form of mineral replacement therapy because of inappropriate renal tubular loss of phosphate and bicarbonate (Skinner et al, 1990;Caron et al, 1992;De Schepper et al, 1993). Renal failure may occur acutely and prevent the delivery of planned chemotherapy, however it is more often a chronic problem with severely affected children suffering from hypophosphataemic rickets, renal tubular acidosis and occasionally nephrogenic diabetes insipidus. Impairment of growth may result from renal tubular acidosis and rickets (De Schepper et al, 1991;Rossi et al, 1992;Skinner et al, 1992). Higher cumulative dose of ifosfamide, younger patient age at treatment (Suarez et al, 1991;Skinner et al, 1992;Al Sheyyab et al, 1993;De Schepper et al, 1993), prior nephrectomy and pre-existing renal impairment, including that caused by prior or concomitant treatment with cisplatin, have all been reported as being associated with an increased risk of ifosfamide-induced nephropathy (Pratt et al, 1991;Suarez et al, 1991;Caron et al, 1992;Skinner et al, 1992;Al Sheyyab et al, 1993;De Schepper et al, 1993), Marina et al, 1993;Tournade, 1993; Rossi et al, 1994a,b).A further possible risk factor is the method of administration of the drug. Schedules of administration in children have varied from short infusions over 15 min to continuous infusion over 3 or more days. One study in adults reported less nephrotoxicity after continuous infusion rather than bolus administration of ifosfamide, but the differences were not statistically significant (Antman et al, 1989). Nephrotoxicity has been documented after all schedules of ifosfamide, and a detailed review found no clear evidence that any schedule showed a significant difference in nephrotoxicity (Skinner et al, 1993). Although both acute and chronic changes have been shown after the administration of ifosfamide, so far there have been no reports of longitudinal studies relating the two.

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Chronic ifosfamide nephrotoxicity in children

Skinner

2003

Med. Pediatr. Oncol.

123

106

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Nephrotoxicity is a frequent complication of treatment with ifosfamide in children. Although renal damage may be acute and reversible, chronic toxicity may develop with potentially serious consequences. Chronic nephrotoxicity due to ifosfamide may lead to a wide variety of subclinical and clinical manifestations. Proximal tubular dysfunction is the commonest presentation, and may lead to a Fanconi syndrome, including hypophosphataemic rickets and proximal renal tubular acidosis. Glomerular impairment is also common, whilst distal tubular impairment has been described but is relatively rare. Although full reversibility has been described occasionally, there is no information about the very long-term outcome of chronic ifosfamide nephrotoxicity. We studied a cohort of 12 children 1 and 10 years after completion of ifosfamide treatment. There was no statistically significant change in either glomerular or tubular toxicity in the group as a whole over this time period. However, marked improvements were seen in some aspects of toxicity in some patients, and deterioration was observed in others. We concluded that considerable nephrotoxicity is still present 10 years after completion of ifosfamide treatment, but that the outcome varies between individual patients. Although several risk factors for the development of chronic nephrotoxicity have been described, total ifosfamide dose, patient age at treatment, previous or concurrent cisplatin treatment, and unilateral nephrectomy are the most important. Nevertheless, it remains difficult to predict the occurrence of this toxicity with confidence. The pathogenesis of ifosfamide nephrotoxicity is poorly understood. There is an urgent need for the development and clinical investigation of nephroprotective strategies.

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Progressive renal toxicity due to ifosfamide

Abstract: A prospective and follow up study of renal tubular and glomerular function in 11 children receiving ifosfamide treatment was con-

Cited by 12 publications

References 2 publications

Progressive glomerular toxicity of ifosfamide in children

Progressive glomerular toxicity of ifosfamide in children

The influence of ifosfamide scheduling on acute nephrotoxicity in children

Chronic ifosfamide nephrotoxicity in children

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