Lithium Nephropathy Treatment & Management

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

The treatment of lithium nephrotoxicity depends on the severity of the toxicity and chronicity as well as the presence of related abnormalities. [32]

The acute lithium nephrotoxicity picture is dominated by evidence of volume depletion, obtundation, and the potential for cardiovascular collapse. These patients will frequently require close monitoring and aggressive fluid replacement even dialysis; therefore, the intensive care unit is the most appropriate site for these patients.

Correcting electrolyte abnormalities in patients with acute disease is critical. Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline). Once volume status is restored, then a forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.

For patients with lesser degrees of lithium toxicity, this therapy will be adequate to treat the condition. For patients with greater degrees of lithium toxicity, generally with lithium levels of greater than 4 mEq/L, dialysis is indicated. Dialysis may also be considered in patients with levels in the mid 2s but who are exhibiting evidence of instability.

The chronic lithium nephrotoxicity picture is dominated by polyuria and evidence of chronic kidney disease. Polyuria can be treated with medications, such as diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs; see Medication).The potassium-sparing diuretic amiloride is the most established therapy for the polyuria associated with lithium use. [33, 17] Amiloride is thought to block lithium uptake into the principal cells of the cortical collecting tubule through epithelial channels (ENaC), allowing the principal cells to regain responsiveness to antidiuretic hormone.

In an animal model of lithium-induced nephrogenic diabetes insipidus, acetazolamide reduced polyuria as effectively as hydrochlorothiazide plus amiloride. Case reports describe successful use of acetazolamide in patients with lithium-induced nephrogenic diabetes insipidus that had failed to respond to treatment with standard agents. [34, 35]

In contrast, a study by de Groot et al in six patients with a lithium-induced urinary concentrating defect found evidence against the use of acetazolamide treatment. Two patients withdrew from the study because of adverse effects, and the remaining four showed no change in urine output or clinically relevant changes in maximal urine osmolality. Three of the four patients experienced an increase in serum creatinine levels, indicating a decreased glomerular filtration rate (GFR). The authors postulate that the reduction in polyuria in animal studies is the result of the decrease in GFR. [36]

The chronic kidney insufficiency can be treated using therapy that would routinely be used for any cause of chronic kidney disease. Evidence of chronic kidney disease is an indication for discontinuation of the drug being administered and for consideration of alternative medications for treatment of the patient's psychiatric disorder. 



See the list below:

  • Endocrinology for evidence of thyroid dysfunction
  • Nephrology for management of aggressive forced diuresis or potential hemodialysis for removal of drug
  • Poison control for updates on the latest treatment guidelines
  • Cardiology for evidence of cardiovascular collapse
  • Psychiatry for evaluation of the ongoing need for lithium therapy or for evaluation of suicidal behavior if apparent