Hypokalemia-Induced Vasopressin Resistance: A Reversible Disorder of Water Homeostasis After Hematopoietic-Cell Transplantation

Introduction: Vasopressin resistance (AVP-R)—formerly nephrogenic diabetes insipidus—is defined by impaired renal response to vasopressin despite preserved secretion. While classically linked to congenital defects or lithium, AVP-R can result from profound electrolyte disturbances. Hypokalemia disrupts aquaporin-2 trafficking in collecting duct principal cells, impairing water reabsorption. We describe a reversible case of AVP-R following autologous hematopoietic cell transplantation (HCT), guided by urine osmolality, copeptin, and bedside ultrasound. Case Description: A 68-year-old woman with kappa light chain multiple myeloma was admitted one week post-HCT with febrile neutropenia. Her course was complicated by mucositis and Clostridioides difficile diarrhea, leading to persistent hypokalemia despite IV repletion. By day 4, she developed hypotonic polyuria (>5 L/day), rising creatinine, and hypernatremia (peak 153 mmol/L) despite continuous free water. Urine osmolality was 205 mOsm/kg. Copeptin was elevated (80 pmol/L), confirming intact vasopressin release and AVP-R. Potassium repletion was intensified using potassium acetate in D5W (60–80 mEq/L at 100–300 mL/hr), delivering potassium, free water, and alkali for concurrent metabolic acidosis. Despite this, hypovolemia persisted. Bedside ultrasound revealed a small, collapsible IVC. Desmopressin (1 mcg IV bid) was given to limit urinary water loss and support intravascular volume, modestly reducing urine output and stabilizing sodium. With sustained normokalemia, urine osmolality rose. Sodium normalized over five days, and copeptin declined to 18 pmol/L. Discussion: This case highlights hypokalemia-induced AVP-R as a reversible complication post-HCT. GI losses and catabolic stress may cause profound potassium depletion. POCUS, copeptin, and urine osmolality provided physiologic clarity, while desmopressin aided management. Tailored potassium acetate in D5W restored water balance and corrected the underlying defect. The 5-day resolution of AVP-R mirrors animal data showing aquaporin-2 recovery within 5–7 days of potassium repletion, supporting its reversibility.