How to adjust lithium (lithium carbonate) dose in a patient with acute kidney injury (AKI) and impaired renal function?

Lithium Dose Adjustment in Acute Kidney Injury

Lithium should be temporarily discontinued in patients with acute kidney injury, as the FDA label contraindicates lithium in patients with significant renal disease due to extremely high risk of toxicity, and KDIGO guidelines specifically recommend temporary discontinuation of lithium during serious intercurrent illness that increases AKI risk. 1, 2

Immediate Management

Discontinue Lithium

• Stop lithium immediately when AKI is diagnosed, particularly in patients with GFR <60 mL/min/1.73m² who develop serious intercurrent illness 1
• The FDA label explicitly contraindicates lithium in patients with significant renal disease, stating "the risk of lithium toxicity is very high in such patients" 2
• Lithium is primarily renally excreted (95%), making dose adjustment unreliable and dangerous in AKI 3, 4

Monitor Lithium Levels Closely

• Check serum lithium levels immediately upon AKI diagnosis and daily thereafter until levels normalize 1
• Lithium toxicity can occur even at therapeutic doses when renal function declines acutely 3, 4
• Monitor for signs of lithium toxicity: tremors, confusion, ataxia, cardiac arrhythmias 3, 4

Clinical Context and Rationale

Why Standard Dose Adjustment is Inadequate

• Unlike chronic kidney disease where dose reduction may be attempted, AKI represents an unstable, rapidly changing clinical scenario 1
• Lithium has a narrow therapeutic index requiring precise dosing based on stable renal function 1
• Water and electrolyte disturbances that commonly accompany AKI are major predisposing factors for lithium toxicity 3
• Renal insufficiency was present in 74% of lithium intoxication cases, with 29% developing permanent renal dysfunction 3

Risk of Continued Use

• Lithium can cause direct tubular epithelial damage, potentially worsening AKI 4
• AKI itself may be lithium-induced (minimal change disease, acute tubular necrosis, or tubulointerstitial nephropathy) 5, 4
• Continued lithium exposure during AKI can lead to severe, potentially irreversible neurological sequelae 3

When Psychiatric Indication is Life-Threatening

Extreme Caution Protocol (Only if No Alternative)

If the psychiatric indication is truly life-threatening and the patient fails all other measures 2:

• Hospitalization is mandatory 2
• Use extremely low doses (typically 25-50% of previous maintenance dose) 2
• Obtain daily serum lithium levels before each dose 2
• Monitor serum creatinine, electrolytes, and volume status daily 1
• Consider psychiatric consultation for alternative mood stabilizers (valproate, carbamazepine, antipsychotics) that are safer in renal impairment

Management of Lithium Toxicity in AKI

If Lithium Levels are Elevated

• Provide aggressive IV hydration with normal saline (if volume status permits) 3
• Do NOT use sodium chloride infusion specifically to enhance lithium excretion, as this has no specific effect and can cause hypernatremia 3
• Consider hemodialysis if serum lithium >4 mmol/L or severe toxicity regardless of level 3

Hemodialysis Considerations

• Hemodialysis is the most effective method for removing lithium in toxicity 3
• Intermittent hemodialysis and prolonged intermittent renal replacement therapy show superior lithium clearance compared to continuous venovenous hemofiltration 6
• Continue dialysis long enough to achieve serum lithium <1 mmol/L after redistribution (lithium redistributes from intracellular to extracellular compartments, causing rebound) 3
• Multiple dialysis sessions may be required due to this rebound effect 3, 4

Recovery and Reintroduction

After AKI Resolution

• Do not restart lithium until renal function returns to baseline or stabilizes 1
• Reassess GFR, electrolytes, and volume status before considering reintroduction 1
• If lithium is restarted, begin at reduced dose (50% of previous) with frequent monitoring 1
• Consider alternative mood stabilizers if AKI was lithium-induced or if patient has residual renal impairment 5

Common Pitfalls to Avoid

• Never attempt simple dose reduction in active AKI—the unpredictable and changing renal clearance makes this dangerous 1, 2
• Do not rely on standard dosing formulas for renal impairment, as these apply to stable chronic kidney disease, not AKI 1
• Avoid combining lithium with other nephrotoxic agents (NSAIDs, ACE inhibitors, diuretics) during recovery phase 1, 7
• Do not assume therapeutic lithium levels are safe—toxicity can occur at therapeutic levels when renal function is impaired 3