Challenges in Identifying and Managing Lithium-Induced Arginine-Vasopressin Resistance

Introduction: Arginine vasopressin resistance (AVP-R), formerly nephrogenic diabetes insipidus, is the inability to concentrate urine due to resistance to AVP. Lithium is a classic cause of AVP-R, but identifying and managing AVP-R is not always textbook. In this case of AVP-R in lithium toxicity, UTI and dysphagia significantly delayed the diagnosis and improvement in symptoms. Case Description: A 71-year-old female with bipolar disorder on chronic lithium, CKD3, and hypertension was admitted for 1 week of confusion, vomiting, and diarrhea. Labs were remarkable for creatinine 3.3mg/dL and sodium 133mEq/L (1 year ago 1.2 and 141 respectively). UA showed a UTI, which was presumed to be the cause of her symptoms. She was given fluids and her Cr improved to 2.5mg/dL. The case seemed closed. Surprisingly, the next day, her sodium was 154mEq/L with >3.5L urine output. Urine osmolality (UOsm) was 189mOsm/kg consistent with water diuresis, triggering a lithium level to be sent. It was 1.92mEq/L, consistent with lithium toxicity given her symptoms. Lithium was held and Nephrology conducted a desmopressin challenge without improvement in her Uosm, confirming AVP-R. She was given ample free water. Despite 5 days without lithium, her UOsm fell to 79mOsm/kg. With amiloride daily, Uosm rose to 137mOm/kg, but for days her sodium continued to fluctuate. HCTZ did not help. Eventually, we noted that she had a thickened liquids diet. The thickener is 5.5g modified food starch with 15mg of sodium in 4oz water. Once she was cleared for thin liquids, her sodium stabilized at 142mEq/L. Unfortunately, 11 days later she continued to have neuro symptoms, requiring inpatient rehab discharge for Syndrome of Irreversible Lithium-Effectuated NeuroToxicity (SILENT). Discussion: This case reveals that lithium induced AVP-R can be masked by volume depletion from UTI and gives evidence that AVP-R can manifest quickly and worsen even after lithium is stopped. Furthermore, it demonstrates how lithium neurotoxicity complicates achieving euvolemia and free water and low solute/protein intake. We found that thickeners add tonicity (and aversion) to otherwise good fluid intake. This case demonstrates the importance of prompt diagnosis and multi-faceted management of lithium toxicities to prevent prolonged hospitalization and permanent life-altering neuromuscular symptoms.