THE ASSESSMENT OF SUBCLINICAL IFOSFAMIDE-INDUCED RENAL TUBULAR TOXICITY USING URINARY-EXCRETION OF RETINOL-BINDING PROTEIN

The excretion of retinol-binding protein in early morning urine sample s, expressed as a ratio to urinary creatinine (RBPCR), was used as a m easure of proximal renal tubular toxicity in children during or after treatment with ifosfamide-containing chemotherapy. The results showed a progressive increase in renal tubular leak after exposure to ifosfam ide that persisted after treatment. The toxic effect appeared to be gr eatest in younger children and at kast partly dose-dependent, although partially reversible after each course of chemotherapy. However, few patients had related symptoms and none experienced major metabolic dif ficulty. RBPCR appears to offer a sensitive and noninvasive way of mon itoring sequential change in renal tubular function after exposure to ifosfamide. Further studies are required to define more clearly the ef fect of cumulative dose, age, and drug scheduling and to identify whet her a level of renal tubular dysfunction, measured by RBPCR or a simil ar noninvasive technique, can identify a threshold beyond which furthe r exposure to ifosfamide is likely to be significantly and permanently damaging.