Lithium Nephropathy Medication

Updated: Jan 18, 2022
  • Author: Eleanor Lederer, MD, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Medication Summary

Diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of stable lithium-induced nephrogenic diabetes insipidus. [37]



Class Summary

Decrease extracellular fluid and promote proximal tubular resorption that is not ADH dependent. Ultimately, less free water is transmitted to distal collecting tubules, which is where the urine-concentrating defect is located; therefore, the polyuria decreases. However, extracellular fluid depletion can also increase the risk of lithium intoxication by enhancing lithium reabsorption at the proximal tubule. Diuretics have a gradual onset of action and are less useful in an acute setting.

Amiloride (Midamor)

Prevents uptake of lithium by epithelial cells. Has less potential for lithium toxicity because has a weak natriuretic effect and is less likely to increase lithium level by causing volume contraction. Has the advantage of being potassium-sparing; hypokalemia itself may potentiate a defect in concentrating ability. Also induces less extracellular fluid contraction than thiazides.

Hydrochlorothiazide (Esidrix)

Thiazides may require potassium supplementation; more often associated with lithium toxicity. Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions. Equivalent dosages of other thiazide preparations may be used. Use same dose range effective for treating hypertension.


Nonsteroidal Anti-inflammatory Drugs

Class Summary

Have an antiprostaglandin effect in rats. Inhibiting prostaglandin increases cAMP in the collecting tubules, which promotes water resorption (see Pathophysiology). NSAIDs also inhibit the production of prostaglandin that regulates glomerular blood flow and therefore decreases the GFR and urine flow to the distal tubules. Physicians do not recommend long-term NSAID therapy.

Indomethacin (Indocin, Indochron ER)

Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis. One case report exists of IV ketorolac used in acutely ill patient failing to respond to indomethacin.