Ifosfamide nephrotoxicity in adult patients

BACKGROUND: Ifosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients. METHODS: The aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity. RESULTS: We report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.