Severe, irreversible renal failure after ifosfamide treatment. A clinicopathologic report of two patients

Abstract

Background: Chronic renal failure has been described only rarely in patients treated with the alkylating agent ifosfamide, which is known to cause renal tubular dysfunction and acute renal failure, and the associated histopathologic features have not been well characterized.

Methods: This report describes the clinical course and renal histopathologic features in two patients in whom irreversible renal failure occurred requiring permanent dialysis after treatment with ifosfamide.

Results: Irreversible renal failure developed in a 60-year-old man with malignant fibrohistiocytoma, requiring chronic dialysis within several months after he received two cycles of ifosfamide in a cumulative dose of 28 g/m2. The second patient, a 53-year-old man with osteogenic sarcoma, received two cycles of ifosfamide with a cumulative dose of 26 g/m2, after initial therapy with cisplatin and doxorubicin. His renal function worsened over the next 11 months, at which time permanent dialysis was initiated. In neither patient were other causes of renal failure apparent. Renal biopsies in both patients showed diffuse tubular epithelial damage with degenerative and regenerative epithelial changes, diffuse interstitial fibrosis, and arterial and arteriolar sclerosis.

Conclusions: Irreversible severe renal failure, which appears due to nephrotoxic damage of renal tubular epithelium and/or the renal microvasculature may develop after treatment with ifosfamide. Neither large cumulative doses of ifosfamide nor prior cisplatin treatment are necessary for this toxicity to occur. Because a rising serum creatinine may develop months after completion of treatment with ifosfamide, renal function should be monitored closely both during and after ifosfamide treatment.