Ifosfamide-induced karyomegalic interstitial nephritis in Ewing’s sarcoma and osteosarcoma: Report of two cases

Ifosfamide (IFO) is a nitrogen mustard alkylating agent, commonly used in the treatment of pediatric solid tumors, including Ewing tumors, osteosarcoma, rhabdomyosarcoma, non-Hodgkin’s lymphoma, as well as acute lymphoblastic leukemia that can cause both acute and chronic kidney injury, with a wide spectrum of clinical manifestations up to end-stage renal disease requiring dialysis. We report two cases of young patients with diagnosis of Ewing’s sarcoma of the chest and ulnar osteosarcoma treated with polychemotherapy including IFO who developed kidney injury. Both patients had IFO-induced karyomegalic interstitial nephritis (KIN) with two different clinical presentations and histological pictures. One patient experienced acute kidney injury a few weeks following IFO chemotherapy, the other 6 months later. the histological examinations revealed interstitial nephritis and karyomegalic cells in both cases. One of them was treated with steroids until remission, the other one with stabilization of kidney function. IFO-induced KIN is a complication of IFO treatment that can be treated with steroids. In general, kidney damage is asymptomatic and renal biopsy is an essential tool in IFO-treated patients to achieve a correct diagnosis and avoid empirical attempts with inappropriate and potentially harmful drugs. IFO tubular toxicity is known but there are other factors, mainly genetic polymorphisms influencing drug metabolism that might increase the susceptibility to kidney damage. The two cases of IFO-induced KIN described here showed different presentations and outcomes.