Ifosfamide nephrotoxicity in adult patients

Abstract

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.

Randomised phase 2 study comparing the efficacy and safety of the oral tyrosine kinase inhibitor nintedanib with single agent ifosfamide in patients with advanced, inoperable, metastatic soft tissue sarcoma after failure of first-line chemotherapy: EORTC-1506-STBSG “ANITA”

“…Ifosfamide-induced nephrotoxicity has been reported to range from 15 to 60% depending on the definition of kidney injury, therapeutic protocols used, and duration of follow-up [33]. A retrospective study in adult patents reported ifosfamideinduced acute kidney injury in 14.4% of patients [33]. In our study, 13.2% of the patients receiving ifosfamide experienced acute kidney injury.…”

“…Acute kidney injury occurs in about 12% of all cancer patients [32]. Ifosfamide-induced nephrotoxicity has been reported to range from 15 to 60% depending on the definition of kidney injury, therapeutic protocols used, and duration of follow-up [33]. A retrospective study in adult patents reported ifosfamideinduced acute kidney injury in 14.4% of patients [33].…”

Investigation of Ifosfamide Toxicity Induces Common Upstream Regulator in Liver and Kidney

“…In clinics, ifosfamide can exert a bimodal antitumor action with cytotoxic and immunomodulatory effects combined with adoptive immunotherapy [12]. Ifosfamide is known to be mainly eliminated by the renal route and about 80% of the dose in the unchanged form, and nephrotoxicity is a commonly known side effect of ifosfamide, and metabolites such as chloroacetaldehyde and acrolein are responsible for its clinical use [13,14].…”

Bendamustine-induced nephrogenic diabetes insipidus – A case report

“…6 There are case reports of Fanconi syndrome combined with NDI that are caused by ifosfamide, another alkylating agent which also acts via a chloroethylamine group. [26][27][28][29][30] The mechanism by which ifosfamide causes NDI is unclear, but the hypokalemia associated with impaired proximal tubular function might be a contributing factor. It is thought that acquired forms of NDI are due to defects or reduced expression of aquaporin 2, a vasopressin-regulated water channel of the collecting duct, but they appear to be reversible after discontinuation of the causing agent.…”