HYPERAMINOACIDURIA IDENTIFIES PATIENTS AT RISK OF DEVELOPING RENAL TUBULAR TOXICITY ASSOCIATED WITH IFOSFAMIDE AND PLATINATE CONTAINING REGIMENS

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 excretion 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 < 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 Debre-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 < .01). HAA characterized by a ratio > 10% predicts the development of a DTFS with a sensitivity of 71.4% and a specificity of 87.4%.