The growing pains of ifosfamide

Abstract

Ifosfamide is a commonly used chemotherapeutic known to have numerous adverse kidney manifestations. In this issue of Clinical Kidney Journal, Ensergueix et al. report a multicentric observational retrospective French study on 34 adult patients with tubular dysfunction and /or kidney dysfunction following ifosfamide treatment. Of these patients, 18% had isolated proximal tubular dysfunction, 14% had isolated acute kidney injury (AKI), 18% had isolated chronic kidney disease (CKD) and 50% had a combination of proximal tubular dysfunction and AKI. Concomitant treatment with cisplatin was identified as a risk factor for the development of AKI, and cisplatin and age were associated with estimated glomerular filtration rate at last follow-up. Interestingly, the cumulative dose of ifosfamide was not associated with renal outcomes. This report highlights the need for additional studies on the prevalence, spectrum and management of ifosfamide-associated nephrotoxicity and clearly demonstrates that patients who received ifosfamide should be followed long term to detect proximal tubular dysfunction and CKD early.

Keywords: Fanconi syndrome; adults; ifosfamide; nephrotoxicity.

FIGURE 1

Mechanism of ifosfamide-associated tubular toxicity. Ifosfamide is transported in the proximal tubular cells through organic cation transporter-2. Ifosfamide undergoes substantial metabolization with the production of acrolein (responsible for bladder irritation and haemorrhagic cystitis) and chloro-acetaldehyde (responsible for the development of proximal tubulopathy). ALDH1A1: aldehyde dehydrogenase 1A1.