What to do next for a 37-year-old (yo) patient with bipolar disorder on lithium, experiencing increased urination and thirst with elevated serum osmolality, who wants to continue lithium therapy?

Management of Lithium-Induced Nephrogenic Diabetes Insipidus

The patient should undergo testing for nephrogenic diabetes insipidus (NDI) with plasma copeptin measurement, as this is the most appropriate next step for a lithium-treated patient with polyuria, polydipsia, and elevated serum osmolality. 1

Diagnostic Assessment

The patient's clinical presentation strongly suggests lithium-induced nephrogenic diabetes insipidus:

• Polyuria and polydipsia (classic symptoms)
• Elevated serum osmolality (306 mOsm/kg)
• Current lithium therapy for bipolar disorder

The diagnostic approach should include:

1. Plasma copeptin measurement - Baseline plasma copeptin levels above 21.4 pmol/l are diagnostic for NDI in adult patients 1

2. If copeptin is <21.4 pmol/l, additional testing is needed:

   • Water deprivation test or hypertonic saline infusion test to differentiate between NDI, central diabetes insipidus, and primary polydipsia 1

3. Laboratory assessment:

   • Urine osmolality (typically inappropriately low despite high serum osmolality)
   • Urinary sodium concentration (typically >40 mEq/L in SIADH, but may be variable in NDI)
   • Serum lithium levels (to ensure therapeutic range)
   • Renal function tests (creatinine, BUN)

Management Strategy

Since the patient wishes to continue lithium therapy, a stepwise approach is recommended:

1. Optimize Lithium Dosing

• Consider reducing lithium dose while maintaining therapeutic effect 2, 3
• Target the lowest effective serum lithium level (0.6-0.8 mmol/L rather than 0.8-1.0 mmol/L) 3
• Split dosing to minimize peak lithium concentrations 2

2. Ensure Adequate Hydration

• Recommend ad libitum access to fluid to prevent dehydration and hypernatremia 1
• Allow the patient to self-regulate fluid intake based on thirst sensation 1
• Monitor weight and serum sodium regularly

3. Consider Pharmacologic Interventions

• Thiazide diuretics (paradoxically reduce polyuria in NDI by promoting proximal tubular water reabsorption)
• Amiloride (can reduce lithium entry into collecting duct cells)
• NSAIDs (can enhance water reabsorption but must be used cautiously due to renal risks)

4. Monitor Renal Function

• Regular monitoring of renal function is essential 2, 4
• Check serum creatinine, eGFR, and urinary concentrating ability every 3-6 months
• Monitor for progression of renal impairment, as long-term lithium use is associated with chronic kidney disease in 21-34% of patients 5, 6

Long-term Considerations

• Lithium-induced NDI can persist even after lithium discontinuation in some cases 6, 7
• The risk of end-stage renal disease is relatively low (approximately 1% after 15+ years of treatment) but requires vigilance 5
• If renal function deteriorates significantly, consider alternative mood stabilizers

Cautions and Pitfalls

1. Avoid dehydration - Patients with NDI are at high risk for lithium toxicity if they become dehydrated 2

2. Medication interactions - NSAIDs, ACE inhibitors, and diuretics can increase lithium levels and toxicity risk 2

3. Recognize early signs of lithium toxicity - Diarrhea, vomiting, drowsiness, muscle weakness, and lack of coordination can occur at serum levels below 2 mEq/L 2

4. Don't confuse with SIADH - Both can present with polyuria/polydipsia, but SIADH typically has hyponatremia rather than the hypernatremia or normal-to-high sodium seen in NDI 1

By implementing this management approach, the patient can potentially continue lithium therapy with minimized renal effects while maintaining effective control of bipolar disorder.