Is lithium nephrotoxic?

Lithium Nephrotoxicity: Evidence and Management

Yes, lithium is nephrotoxic and can cause both acute and chronic kidney damage with prolonged use, even at therapeutic levels. 1, 2

Mechanisms and Types of Lithium-Induced Kidney Damage

• Lithium can cause nephrogenic diabetes insipidus with polyuria and polydipsia, which is usually reversible when lithium is discontinued 2
• Chronic lithium therapy is associated with morphologic changes including glomerular and interstitial fibrosis and nephron atrophy 2
• Long-term lithium treatment can lead to chronic kidney disease (CKD) and, in rare cases, end-stage renal disease (ESRD) 3
• Kidney function decline occurs gradually, with yearly increases in median serum creatinine levels observed from the first year of treatment 4

Prevalence and Risk Factors

• Approximately one-third of patients who have taken lithium for 10-29 years develop signs of chronic renal failure, though only 5% fall into severe or very severe categories 4
• The percentage of patients with eGFR <60 ml/min/1.73 m² (grade 3 CKD) is significantly higher in lithium-treated patients (34.4%) compared to controls (13.1%) 5
• Risk factors for lithium nephrotoxicity include:
  • Duration of therapy (longer exposure increases risk) 6, 7
  • Episodes of lithium toxicity or elevated lithium levels 7
  • Increasing age 7
  • Concomitant use of other nephrotoxic medications, particularly NSAIDs 1

Monitoring and Management Recommendations

• All people taking lithium should have their GFR, electrolytes, and drug levels regularly monitored 1
• Monitoring should occur at least every 6 months, or more frequently if dose changes or the patient becomes acutely ill 1
• Baseline kidney function assessment should be performed prior to starting lithium therapy 2
• Progressive or sudden changes in renal function, even within normal range, indicate the need for treatment reevaluation 2
• Lithium should be temporarily discontinued during serious intercurrent illness that increases the risk of acute kidney injury 1

Precautions and Preventive Measures

• Avoid concomitant use of NSAIDs in patients taking lithium 1
• Maintain adequate hydration, particularly during intercurrent illness 1
• Consider using lower lithium plasma level targets for long-term maintenance to reduce the risk of severe nephrotoxicity 3
• Carefully manage patients with polyuria and polydipsia to avoid dehydration with resulting lithium retention and toxicity 2

Clinical Decision-Making Algorithm

1. Before initiating lithium:

   • Assess baseline kidney function (eGFR, urinalysis) 2
   • Evaluate for pre-existing kidney disease or risk factors

2. During lithium treatment:

   • Monitor serum lithium levels, GFR, and electrolytes every 6 months 1
   • Increase monitoring frequency with dose changes or acute illness 1
   • Assess for symptoms of nephrogenic diabetes insipidus (polyuria, polydipsia) 2

3. If kidney function declines:

   • For mild decline: Consider risk-benefit of continuing lithium versus switching to alternative mood stabilizer 7
   • For moderate decline (eGFR 30-60 ml/min/1.73 m²): Consider nephrology consultation and closer monitoring 1
   • For severe decline (eGFR <30 ml/min/1.73 m²): Strongly consider alternative mood stabilizers if clinically appropriate 7

4. During acute illness:

   • Temporarily suspend lithium 1
   • Monitor kidney function and lithium levels more frequently 1
   • Ensure adequate hydration 1

Important Caveats

• Nephrogenic diabetes insipidus symptoms (polyuria) only weakly predict declining kidney function 3
• Kidney function may continue to deteriorate even after lithium cessation in some patients 3
• The risk-benefit of lithium must be carefully weighed in each specific situation, as it remains the most efficacious treatment for bipolar disorder despite nephrotoxicity concerns 1, 7
• ESRD is a rare complication, affecting approximately 1% of patients who have taken lithium for over 15 years 5