ODP336 Nephrogenic Diabetes Insipidus and Fanconi Syndrome Induced by Ifosfamide in a Patient with Femur Osteosarcoma. A Case Report
Authors: Ramos-Torres Guillermo , Concepción-Zavaleta Marcio Marcio , Ildefonso-Najarro Sofía , Plasencia-Dueñas Esteban , Gonzãles-Yovera Jhean , Alcalde-Loyola Carlos , Concepción-Urteaga Luis , Ramos-Yataco Anthony , Paz-Ibarra José , Correa Ricardo , Roseboom Pela 
Published: November 2022

Abstract

Background
Fanconi syndrome and diabetes insipidus are rare adverse effects of ifosfamide. They usually present with high cumulative doses of this medication. They are mainly related to type II proximal renal tubular dysfunction. These complications typically present with severe polydipsia and polyuria accompanied by glycosuria, proteinuria, and some electrolyte abnormalities including hypokalemia, hypophosphataemia, and non-anion gap metabolic acidosis. Clinical case: A 15-year-old male with, a diagnosis of metastatic osteoblastic osteosarcoma in the right distal treated with ifosfamide three years prior to this hospitalization, was admitted to the emergency department complaining of 3 episodes of vomiting, 6 days history of increase volume of the right lower limb and fever. On admission, blood pressure of 80/50 mm Hg, heart rate of 110 beats / minute, respiratory rate of 30 breaths / minute, axillary temperature of 38.3 ° C. It was evident phlogosis at level of the proximal third of the right lower limb. CBC revealed pancytopenia (WBC 5 x10 9 L, Hb 6.8 g/dL, platelets 25×10 3 /mm 3) and ABG and CMP were compatible with mild metabolic acidosis normal AG (pH 7.285, K 1.9 meq / L, Na 156 meq / L, lactate: 0.9 meq / L, HCO3: 17 meq / L). A diagnosis of sepsis was made and the patient was started on meropenem 2g IV every 8 hours, vancomycin 1 g IV every 12 hours, filgastrim 120 ug/daily and one unit of packed RBC. Patient improved after 5 days over the course of his hospitalization. However, on the 18 th day after his hospital admission, he developed a new episode of polyuria, associated with hypocalcemia (7 mg/dL), hypokalemia (2 mEq/L), hypomagnesemia (0.95 mg/dL), hypophosphatemia (0.9 mg/dL) and metabolic acidosis (pH 7.2, bicarbonate 15 mEq/L). Urine analysis revealed glucosuria and proteinuria. Desmopressin test did not showed increase urinary osmolarity thus nephrogenic diabetes insipidus and Fanconi syndrome were diagnosed due to the multiple laboratory abnormalities and sign/symptoms. Patient received electrolyte replacement and ifosfamide was stopped from his chemotherapy regimen. After this, patient recovers and he was discharge at 25 th day of his admission.

Conclusion
: Ifosfamide causes tubular cell dysfunction leading to both nephrogenic diabetes insipidus and Fanconi syndrome. These complications might event present several years after receiving this chemotherapeutic agent. Full electrolyte repletion and hydration are the gold standard for management The present case report emphasizes the importance of the prevention of nephrotoxicity associated with ifosfamide, since its presentation could increase poor outcomes in patients receiving chemotherapy regimens that include ifosfamide.
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