Development of ifosfamide-induced nephrotoxicity: Prospective follow-up in75 patients

Purpose. This study was performed to describe prospectively the development and prognosis of severe ifosfamide-induced nephrotoxicity and to define th e period of recommended renal follow-up after ifosfamide chemotherapy. Pati ents and Methods. Renal function was followed in 75 patients after cessatio n of chemotherapy starting within the first year off therapy; median follow -up time was 31 months. The glomerular filtration rate was estimated by usi ng the Schwartz formula. Proximal tubular transport capacities were evaluat ed for amino acids, phosphate, sodium, and glucose. In addition, serum bica rbonate level and alkaline phosphatase were measured. Results. Five patient s developed renal Fanconi syndrome during follow-up, and another seven pati ents developed a generalized subclinical tubulopathy. The latter condition always preceded Fanconi syndrome. Severe impairment of amino acid and phosp hate reabsorption was seen in 28% and 17.3% of patients, respectively. Redu ctions in amino acid reabsorption preceded impairment of phosphate reabsorp tion. In patients with early impairment of phosphate reabsorption, renal pr ognosis was poor, whereas normal or only mildly impaired amino acid handlin g virtually excluded progressive tubular damage. Conclusions. Ifosfamide-in duced renal tubular damage is a potentially progressive disease. Along with measurement of phosphate reabsorption, additional assessment of tubular am ino acid handling is suggested, because it allows early discrimination of p oor from favorable renal outcomes. (C) 1999 Wiley-Liss, Inc.