Abstract: FR-PO0908
Drug-Induced Hypokalemia Causing Nephrogenic Diabetes Insipidus: A Case of Dual Nephrotoxicity from Ifosfamide and Foscarnet
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 1
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Eskander, Kirollos, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Singh, Aditi, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Coombs, Nickolas, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Gross, Matthew William, Johns Hopkins Medicine, Baltimore, Maryland, United States
Introduction
Nephrogenic diabetes insipidus (NDI) is an underappreciated complication of chronic hypokalemia. Both ifosfamide and foscarnet cause renal potassium wasting, yet their combined contribution to NDI has not been described.
Case Description
A 26-year-old female with Hodgkin's lymphoma, status post multiple lines of therapy including ifosfamide (initiated 2021) and peripheral blood stem cell transplant, was started on foscarnet for resistant herpes simplex virus in 2025. Nephrology was consulted for polyuria (up to 6 L/day), severe recurrent hypokalemia (nadir 1.9 mmol/L), hypomagnesemia, and hypophosphatemia which began intermittently since 2021 and persistent after foscarnet initiation in 2025. 24-hour urine collection confirmed renal potassium (110mmol) and magnesium wasting (145 mg). Diuretic screen was negative. Elevated copeptin (31.6 pmol/L) with serum sodium of 147 mmol/L confirmed NDI. Polyuria resolved with correction of hypokalemia supporting the diagnosis of inducing NDI.
At discharge, management included potassium chloride 120 mEq four times daily, magnesium oxide 400 mg twice daily, and amiloride 5 mg daily.
Discussion
This case illustrates a dual-hit mechanism of drug-induced NDI. Ifosfamide causes proximal tubular injury via its metabolite, chloroacetaldehyde, leading to Fanconi syndrome with potassium, phosphate, and magnesium wasting. Foscarnet independently causes potassium wasting primarily through magnesium depletion. Together, they led to chronic hypokalemia triggering NDI.
Molecularly, hypokalemia triggers autophagic degradation of aquaporin-2 (AQP2), leading to vasopressin resistance in the collecting ducts. While these agents' nephrotoxicity can be irreversible (more commonly seen with ifosfamide than foscarnet), hypokalemia-induced NDI is reversible with potassium repletion, consistent with our patient's clinical improvement. Elevated copeptin (>21.4 pmol/L) reliably differentiates NDI from other causes of polyuria and polydipsia. Aggressive potassium repletion and potassium-sparing agents are central to management.