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Lithium NDI Amiloride Thiazide Treatment — ESENeph MCQ

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ModerateTubular DisordersLithium NDI Amiloride Thiazide TreatmentESENeph

A 22-year-old man presents with polyuria (5 L/day) and polydipsia. Serum sodium is 148 mmol/L, serum osmolality 305 mOsm/kg, urine osmolality 180 mOsm/kg. After desmopressin 2 mcg IM, urine osmolality rises to 210 mOsm/kg (incomplete response). He has been taking lithium for bipolar disorder for 4 years. What is the most appropriate treatment for his polyuria?

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Correct answer: C — Hydrochlorothiazide with amiloride

Lithium-induced nephrogenic diabetes insipidus (NDI) is caused by lithium accumulation in principal cells of the collecting duct, downregulating aquaporin-2 expression via inhibition of glycogen synthase kinase-3. The incomplete response to desmopressin confirms nephrogenic (not central) DI. Amiloride is the specific treatment — it blocks ENaC, preventing lithium entry into principal cells. Combining with a thiazide creates a mild volume contraction that enhances proximal sodium and water reabsorption, reducing distal delivery and urine output. Lithium should only be stopped with psychiatric input due to relapse risk. Tolvaptan would worsen the condition.

Reference: Grünfeld & Rossier 2009 – Lithium NDI Pathophysiology; NICE 2014 – CG185 Bipolar Disorder