Children’s toxicology from bench to bed - Drug-induced Renal Injury (2): Nephrotoxiciy induced by cisplatin and ifosfamide in children

Abstract

Cisplatin and carboplatin cause dose-dependent renal dysfunction. Electrolyte abnormalities such as hypomagnesaemia and hypokalemia are commonly reported adverse effects, in addition to increased serum creatinine and uremia. Cumulative dose, dehydration, hypoalbuminemia, and concurrent use of nephrotoxic drugs have been suggested as risk factors for cisplatin nephrotoxicity. The adverse effects of ifosfamide include proximal tubular damage, and renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have also been reported with ifosfamide treatment. Risk factors for ifosfamide nephrotoxicity include the cumulative dose, young age, previous or concurrent cisplatin treatment, and unilateral nephrectomy. Ifosfamide/Carboplatin/Etoposide (ICE) combination therapy induces hypouricemia, which frequently includes renal wasting of electrolytes, and persistent hypouricemia has been observed in recurrent or chemotherapy-resistant patients. We retrospectively examined the incidence of hypouricemia and clinical findings in pediatric patients treated with an ICE regimen. Twenty of 28 (71.4%) pediatric patients had hypouricemia. The duration of hypouricemia was longer in the non-remission subgroup of patients, which suggests that hypouricemia may be a predictive marker for prognosis of malignant disease and efficacy of drugs such as ifosfamide, carboplatin and cisplatin. Nephrotoxicity induced by these drugs may also be more common in pediatric patients than in adults, but it is unclear why a young age is a risk factor and further research is required regarding the mechanism of antineoplastic drug induced-nephrotoxicity in children.