A 60-year-old woman on long-term lithium for bipolar disorder develops nephrogenic diabetes insipidus (NDI). Serum sodium is 152 mEq/L. Urine osmolality is 180 mOsm/kg after water deprivation. Which is the MOST appropriate treatment to reduce urine output in lithium-induced NDI?
- A Desmopressin (DDAVP) high dose
- B Amiloride ✓
- C Hydrochlorothiazide alone
- D Indomethacin
Explanation
Lithium enters collecting duct principal cells via ENaC and inhibits aquaporin-2 (AQP2) upregulation by ADH. Amiloride blocks ENaC, reducing lithium entry into collecting duct cells and partially restoring AQP2 expression — making it the treatment of choice for lithium-induced NDI when lithium must be continued. Desmopressin is ineffective in NDI by definition (the collecting duct is unresponsive to ADH). Thiazides work by inducing mild volume contraction reducing GFR, but amiloride is specifically preferred in lithium-induced NDI. Indomethacin can reduce urine volume but carries GI and renal risks.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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