Néphrotoxicité de l’ifosfamide

Abstract

Ifosfamide is a cytotoxic drug usually used in malignant sarcomas. The nephrotoxicity of this agent has been described essentially among children, revealed by renal failure and proximal tubulopathy. We recently conducted a retrospective multicentre study, describing 34 adult patients admitted for ifosfamide nephrotoxicity. More than 80% of them presented with renal failure, diagnosed up to 48 months after ifosfamide administration. A Fanconi syndrome with hypophosphoremia, hypokaliemia, glucosuria and low-molecular weight proteinuria, was present in two third of all cases. Median estimated glomerular filtration rate was 31mL/min 1 month and 38mL/min 3 months after ifosfamide infusion, versus 67mL/min at baseline. Renal biopsy, performed in 14 of these patients, showed acute tubular necrosis with vacuolization of proximal tubular epithelial cells with marked nuclear modifications, whereas electron microscopy revealed major changes of mitochondrial structure inside those cells, suggesting a tenofovir-like mechanism of nephrotoxicity. After a median follow-up of 31 months, ten patients out of 34 reached stage 5 chronic kidney disease, requiring dialysis in five cases. Poor renal prognosis was associated with concomitant cisplatin use (P=0.02) and with older age at presentation (P=0.04). In conclusion, ifosfamide nephrotoxicity is often severe and irreversible, leading to proximal tubulopathy and sometimes-severe chronic kidney failure, that can be immediate or delayed, sometimes diagnosed months after chemotherapy completion.