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 samples, expressed as a ratio to urinary creatinine (RBPCR), was used as a measure 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 ifosfamide that persisted after treatment. The toxic effect appeared to be greatest in younger children and at least partly dose-dependent, although partially reversible after each course of chemotherapy. However, few patients had related symptoms and none experienced major metabolic difficulty. RBPCR appears to offer a sensitive and noninvasive way of monitoring sequential change in renal tubular function after exposure to ifosfamide. Further studies are required to define more clearly the effect of cumulative dose, age, and drug scheduling and to identify whether a level of renal tubular dysfunction, measured by RBPCR or a similar noninvasive technique, can identify a threshold beyond which further exposure to ifosfamide is likely to be significantly and permanently damaging.