title: Hyperaminoaciduria identifies patients at risk of developing renal tubular toxicity associated with ifosfamide and platinate containing regimens.
abstract: We monitored renal tubular function in 18 neuroblastoma patients treated with chemotherapeutic regimens containing Ifosfamide and platinates. The total IFO dose ranged from 30 to 48 g/m2. After each IFO course and at regular intervals during follow-up 24 hour urinary exception of aminoacids, qualitative excretion of protein and glucose, tubular reabsorption of phosphate, serum pH, and liver enzyme (SGOT and SGPT) were measured. The ratio of alpha-amino-Nitrogen/total-Nitrogen (normal less than 2.5%) and the urinary excretion pattern were used to quantify the aminoaciduria in 12 out of 15 evaluable patients some degree of tubular toxicity occurred during treatment, slowly progressing to a Debré-de Toni-Fanconi syndrome (DTFS) in 7 patients. The DTFS was fully developed in most cases 3-9 months after the end of treatment and was reversible in 3 cases. Hyperaminoaciduria (HAA) occurred in all patients during treatment, preceding other signs of tubular toxicity. The maximum ratio measured before development of a DTFS was significantly higher in the patients with severe toxicity (P less than .01). HAA characterized by a ratio greater than 10% predicts the development of a DTFS with a sensitivity of 71.4% and a specificity of 87.4%.
authors.affiliation: Department of Pediatric Oncology, Emma Kinderziekenhuis/Children's Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: H N
authors.initials: HN
authors.lastname: Caron
authors.forename: N
authors.initials: N
authors.lastname: Abeling
authors.forename: A
authors.initials: A
authors.lastname: van Gennip
authors.forename: J
authors.initials: J
authors.lastname: de Kraker
authors.forename: P A
authors.initials: PA
authors.lastname: Voûte
mesh_terms: D000410:Alanine Transaminase / Q000187:drug effects; D000596:Amino Acids / Q000652:urine*; D001219:Aspartate Aminotransferases / Q000187:drug effects; D016190:Carboplatin / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects*; D007223:Infant; D007674:Kidney Diseases / Q000150:complications*; D007684:Kidney Tubules / Q000187:drug effects*; D008099:Liver / Q000187:drug effects; D010710:Phosphates / Q000652:urine
chemical_list: D000596:Amino Acids; D010710:Phosphates; D016190:Carboplatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002945:Cisplatin; D007069:Ifosfamide