Renal · Year 2 · from Renal
Case 2: Lithium-Induced Nephrogenic Diabetes Insipidus
Patient Presentation
A 52-year-old male with bipolar disorder on lithium therapy for 15 years presents with polyuria, polydipsia, and fatigue. He reports urinating 10-12 times daily and waking 3-4 times at night to void.
History of Present Illness
- Lithium 600 mg twice daily for 15 years
- Gradual onset of increased urination over 5 years
- Drinks 4-5 liters of fluid daily
- Nocturia disrupting sleep
- No change in mental status
Physical Examination
- Blood pressure: 134/82 mmHg
- Heart rate: 78 bpm
- Mild dry mucous membranes
- No edema
- Mental status normal
Workup
Laboratory Studies:
- Serum sodium: 147 mEq/L (elevated)
- Serum osmolality: 305 mOsm/kg (elevated)
- Lithium level: 0.9 mEq/L (therapeutic)
- Urine osmolality: 180 mOsm/kg (inappropriately dilute)
- Serum ADH level: 8 pg/mL (elevated - appropriate response to hyperosmolality)
Water Deprivation/DDAVP Test:
- After water deprivation: Urine osmolality 190 mOsm/kg
- After DDAVP: Urine osmolality 210 mOsm/kg (minimal response)
Diagnosis
Lithium-Induced Nephrogenic Diabetes Insipidus
Discussion
This case illustrates impaired concentrating ability:
- Lithium Mechanism: Lithium enters collecting duct cells through ENaC and accumulates, interfering with ADH signaling and reducing AQP2 expression. Over years, this becomes irreversible.
- Nephrogenic DI Features: Unlike central DI, ADH levels are elevated (appropriate response to hyperosmolality), but the kidney cannot respond. DDAVP administration does not improve concentration.
- Partial Concentrating Defect: The urine is not maximally dilute (50 mOsm/kg) but cannot concentrate above ~200 mOsm/kg, indicating partial but not complete damage to the concentrating mechanism.
Treatment
- Psychiatry consultation regarding alternative mood stabilizers
- If lithium must continue: Amiloride 5-10 mg daily (blocks ENaC, reducing lithium entry into collecting duct cells)
- Thiazide diuretics (paradoxically reduce urine volume by inducing mild volume contraction)
- Low-sodium, low-protein diet to reduce solute load
- Ensure adequate free water access
Clinical Pearl
Amiloride is uniquely useful in lithium-induced NDI because it blocks ENaC, the channel through which lithium enters collecting duct principal cells. This reduces intracellular lithium accumulation while maintaining therapeutic serum lithium levels.