Summary The purpose of the study was to evaluate the incidence, risk factors and changes in severity with time of cisplatin nephrotoxicity in children. A total of 35 children underwent measurement of glomerular filtration rate (GFR) and tubular function after completion of cisplatin chemotherapy. No child received ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and serum magnesium. Followup studies were performed in 16 children at 1 year and in 15 at 2 years after cisplatin. Considerable interpatient variability in nephrotoxicity was observed. Treatment was modified in three patients because of nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity caused hypomagnesaemia in ten patients and hypocalcaemia in five patients. Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30 children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe in children who received cisplatin courses at a dose rate of 40 mg m-2 dar' than in those who received higher dose rates (P < 0.005), but there was no correlation with total dose received. Follow-up studies revealed partial recovery of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in children treated with cisplatin, and more severe at higher dose rates. Despite partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown and careful monitoring of chronic toxicity is necessary.Keywords: cisplatin; nephrotoxicity; children The use of combination chemotherapy has led to dramatic improvements in the survival rates from many childhood malignancies during the last three decades. However, cytotoxic drugs may also cause severe and chronic side-effects, leading to permanent ill-health, disability or even premature death (Morris Jones and Craft, 1990). The development of effective strategies to prevent these adverse events depends on careful evaluation of toxicity both during and after treatment.In view of its established efficacy, cisplatin has retained an important role in the treatment of several childhood solid tumours, including neuroblastoma, osteosarcoma, hepatic and brain tumours, despite the increasing use of its apparently less nephrotoxic analogue carboplatin. Indeed, recent evidence has suggested that cisplatin may be more active than carboplatin in some germ cell tumours in adolescents and adults (Bajorin et al, 1993). However, even with the use of hyperhydration and other protective measures, nephrotoxicity is still a common and potentially serious adverse effect of cisplatin in both adults (Madias and Harrington, 1978;Schilsky et al, 1982;Daugaard and Abildgaard, 1989) and children (Womer et al, 1985;Brock et al, 1991). Despite numerous publications concerning cisplatin nephrotoxicity in adults, there is less information and no clear consensus on the importance of patient-and treatment-related risk factors for the development of nephrotoxicity in children. Furthermore, as there are few data concerning the long-term outcome of cisplatin nep...
Summary This study investigated changes and the time course of these changes in renal function in children following treatment with carboplatin, and identified risk factors for nephrotoxicity. Glomerular and proximal renal tubular function were investigated before and up to 2 years after treatment in 23 children who received carboplatin. The main findings were reduced glomerular filtration rate (GFR), and increased renal tubular loss of magnesium, manifested by a low serum magnesium (S Mg). The mean fall in GFR was 22 ml min -1 1.73 m -2 (P = 0.012), and in S Mg it was 0.17 mmol l -1 (P = 0.0077). No patient had a clinically important reduction in GFR, and only one patient had symptomatic hypomagnesaemia. GFR and S Mg did not change over time after completion of treatment. Cumulative dose (CD) of carboplatin was inversely related to mean S Mg at the end of treatment (P = 0.031), and directly related to the fall in S Mg (P < 0.001). Calculated cumulative area under the plasma concentration versus time curve (AUC) of carboplatin was inversely related to S Mg after treatment (P = 0.004). Dose intensity (DI) of carboplatin was not shown to be related to S Mg following treatment. CD, AUC and DI of carboplatin were not related to GFR, nor change in GFR, after treatment. High CDs of carboplatin may be associated with evidence of renal damage qualitatively similar to but less severe than that caused by cisplatin. GFR and SMg should be carefully monitored when high CDs of carboplatin are used, or if carboplatin is combined with other nephrotoxic chemotherapy.
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