Abstract Introduction Ifosfamide is an alkylating chemotherapeutic agent widely used in treating hematologic and solid malignancies. While nephrotoxicity is well-recognized, arginine vasopressin resistance (AVP-R, formerly nephrogenic diabetes insipidus) represents an uncommon but potentially severe complication with few cases reported in the literature. Early recognition is essential to prevent life-threatening dehydration and electrolyte disturbances, particularly in immunocompromised patients. For clarity, the updated nomenclature distinguishes AVP-R from arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus). Case Description A 57-year-old man with chronic lymphocytic leukemia and Richter’s transformation to diffuse large B-cell lymphoma, previously treated with allogeneic stem cell transplantation, presented with fever, splenomegaly, and progressive cytopenias concerning for hemophagocytic lymphohistiocytosis. He was treated with RICE chemotherapy including ifosfamide.During hospitalization, the patient developed persistent fevers, hypotension, and severe pancytopenia requiring broad-spectrum antimicrobials and transfer to the step-down unit for vasopressor support due to hemodynamic instability. Forty-eight hours after ifosfamide administration, he developed dramatic polyuria with urine output exceeding 10 liters within 24 hours. Laboratory evaluation revealed urine osmolality of 330 mOsm/kg with normal serum osmolality, absence of hyperglycemia or glycosuria, and stable serum electrolytes, consistent with AVP-R. Nephrology consultation confirmed ifosfamide-induced nephrotoxicity as the most likely etiology.Management consisted of aggressive intravenous fluid replacement to maintain euvolemia and midodrine for blood pressure support. Vasopressors were successfully weaned over several days. Desmopressin was not started as the intermediate urine osmolality suggested retained partial collecting duct responsiveness to arginine vasopressin. Discussion Ifosfamide nephrotoxicity is largely mediated by its metabolite chloroacetaldehyde, which damages renal tubular cells. While proximal tubular dysfunction is well described, distal tubular injury leading to AVP-R is rare. Reported cases demonstrate variable responsiveness to desmopressin, reflecting partial resistance of the collecting ducts to arginine vasopressin. In this patient, recent exposure to high dose ifosfamide combined with critical illness likely increased tubular susceptibility to injury.This case emphasizes AVP-R as an uncommon but serious manifestation of ifosfamide toxicity. Close monitoring of urine output and osmolality in patients receiving ifosfamide is warranted, particularly in hematology and oncology populations where nephrotoxic exposures and hemodynamic instability are frequent. Early recognition allows timely supportive management and may prevent severe complications. This abstract is funded by: None
Mustafa et al. (Fri,) studied this question.