Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate

We investigated the renal function of pediatric and adult patients who had been submitted to chemotherapy with high-dose methotrexate (MTX), cisplatin and high-dose ifosfamide (IFO). We observed 43 osteosarcoma patients aged 4-34 years (median 16 years). The median received cumulative doses of MTX, cisplatin and IFO were 60.1 g/m², 598 mg/m² and 73.5 g/m². Renal function was assessed by measurement of creatinine clearance, renal threshold for phosphate (Tmp/GFR), urinary α₁-microglobulin (A1M):creatinine ratio, urinary albumin:creatinine ratio, 24-h glycosuria and proteinuria. The median interval between chemotherapy completion and first renal function assessment was 2 months (range 2-4 months); assessments were then performed at a median interval of 16 months (range 9-49 months). A significant decrease of TmP/GFR was observed only in the pediatric group (under 18 years): the percentage of patients with TmP/GFR <1 mmol/l increased from 21% (six of 28) at the end of treatment to 46% (13 of 28) at the late assessment. Glycosuria in 10 (67%) of 15 adults and 21 (75%) of pediatric patients was detected with an increased incidence compared to the early post-chemotherapy assessment (13% adults and 29% children). A significant increase of the albumin:creatinine ratio and A1M:creatinine ratio was observed only in adults. Overall, 21 patients had a reduced glomerular function at the latest evaluation, associated with glycosuria in 15 patients (71%), proteinuria in 14 (67%) and TmP/GFR <1 mmol/l in 11 (52%). We conclude that strict monitoring of renal function should be recommended in pediatric and adult patients after chemotherapy with high-dose MTX, cisplatin and high-dose IFO.