ACUTE CHANGES IN URINE PROTEIN EXCRETION MAY PREDICT CHRONIC IFOSFAMIDE NEPHROTOXICITY - A PRELIMINARY OBSERVATION

Purpose: To evaluate proteinuria occurring early after ifosfamide ther apy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. Methods: One-dimensional sodium dode cyl sulphate polyacrylamide gel electrophoresis was used to characteri ze urine protein excretion in 12 children with solid tumours before an d after the first course of ifosfamide treatment, and in 24 healthy ch ildren. Chronic nephrotoxicity was evaluated at 6 months after ifosfam ide treatment and graded as none, mild, moderate or severe. Results: U rine from healthy children and from 10 of 12 patients before ifosfamid e therapy showed a protein band with a molecular weight (95.4 kDa) cor responding to that of Tamm-Horsfall protein but no lower molecular wei ght proteins. After the first course of ifosfamide this 95.4-kDa prote in was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (< 70 kDa) in eight. Tamm-Horsfall pr otein was lost in two of five patients who subsequently developed no o r mild nephrotoxicity and in four of five patients who subsequently de veloped moderate or severe nephrotoxicity. Conclusions: Early subclini cal changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subse quent chronic nephrotoxicity.