Assessment of chemotherapy-associated nephrotoxicity in children with cancer

Skinner, Roderick; Pearson, Andrew D.J.; Coulthard, Malcolm; Skillen, A. W.; Hodson, A. W.; Goldfinch, M.; Gibb, I; Craft, Alan

doi:10.1007/bf00689694

Cited by 59 publications

(47 citation statements)

References 57 publications

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“…The study protocol was approved by the Joint Ethics Committee of Newcastle Health Authority and the University of Newcastle upon Tyne, and allowed assessment of glomerular, proximal and distal renal tubular function (Skinner et al, 1991).…”

Section: Investigation and Grading Of Nephrotoxicitymentioning

confidence: 99%

“…The HCO 3 was also measured. The fractional excretions of sodium, potassium, calcium, magnesium, phosphate (FEp), glucose (FEg) and urate, and the renal tubular threshold for phosphate (Tm p /GFR) were calculated using standard formulae (Skinner et al, 1991). The fractional excretion of a substance is the percentage of the filtered load at the glomerulus that is subsequently excreted in the urine; an abnormally high fractional excretion indicates reduced tubular reabsorption.…”

Section: Proximal Tubular Functionmentioning

confidence: 99%

“…Previously outlined normal ranges were used for age-or sexdependent measures of toxicity, including biochemical variables (serum concentrations of creatinine, bicarbonate, phosphate and magnesium; and Tm p /GFR) (Skinner et al, 1991), and systolic blood pressure (Children, 1987) (Table 2). (Clayton et al, 1980;Brodehl et al, 1982;Skinner et al, 1991).…”

Section: Normal Rangesmentioning

confidence: 99%

“…(Clayton et al, 1980;Brodehl et al, 1982;Skinner et al, 1991). **See text (Methods) (Skinner et al, 1991).…”

Section: Normal Rangesmentioning

confidence: 99%

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2000

Br J Cancer

108

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The aim of this multicentre study was to document the nephrotoxicity associated with ifosfamide and evaluate risk factors in 148 children and young people with sarcomas who underwent investigation of renal function on one occasion each, at a median of 6 (range 1–47) months after completion of ifosfamide (median dose 62.0 (range 6.1–165.0) g/m 2 ). Investigations included glomerular filtration rate (GFR), serum bicarbonate (HCO 3 ) and phosphate (PO 4 ), and renal tubular threshold for phosphate (Tm p /GFR). A clinically relevant ‘nephrotoxicity score’ was derived. GFR was < 90 ml/min/1.73 m 2 in 61 of 123 evaluable patients, Tm p /GFR < 0.9–1.1 mmol/l (age-dependent) in 45/103, serum PO 4 < 0.9–1.mmol/l (age-dependent) in 28/135, and serum HCO 3 < 20 (< 18 in infants) mmol/l in 22/95. Of 76 fully evaluable patients: 50% had mild, 20% moderate and 8% severe nephrotoxicity. Higher total ifosfamide dose correlated significantly with greater glomerular and tubular toxicity ( P < 0.01); other risk factors, including age at treatment, demonstrated no consistent significant independent effect. Chronic ifosfamide-related glomerular and proximal tubular toxicity were common in this large comprehensive study. Restriction of total ifosfamide dose to < 84 g/m 2 will reduce the frequency of, but not abolish, clinically significant nephrotoxicity, whilst doses > 119 g/m 2 are associated with a very high risk of severe toxicity. © 2000 Cancer Research Campaign

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Section: Investigation and Grading Of Nephrotoxicitymentioning

confidence: 99%

Section: Proximal Tubular Functionmentioning

confidence: 99%

Section: Normal Rangesmentioning

confidence: 99%

“…(Clayton et al, 1980;Brodehl et al, 1982;Skinner et al, 1991). **See text (Methods) (Skinner et al, 1991).…”

Section: Normal Rangesmentioning

confidence: 99%

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2000

Br J Cancer

108

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“…We have previously described a protocol to assess glomerular and proximal and distal renal tubular function (Skinner et al, 1991). Serum creatinine (S Creat) was used because of the practical and ethical difficulties of performing three plasma [51Cr]EDTA clearances within 3 weeks to assess glomerular function when not clinically necessary.…”

Section: Measures Of Nephrotoxicitymentioning

confidence: 99%

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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