What is the incidence of impaired renal function with lithium use?

Renal Damage with Lithium Use: Incidence and Monitoring

Renal damage is common with long-term lithium use, affecting approximately one-third of patients who take lithium for 10-29 years, though only about 5% develop severe or very severe renal impairment. 1

Incidence and Progression of Renal Impairment

• Chronic kidney disease (CKD) occurs at a rate of 0.012 cases per exposed patient-year in lithium-treated patients 2
• Average decline in estimated glomerular filtration rate (eGFR) is approximately 1.8 ml/min/year in patients who develop CKD stage 3 2
• Approximately 34.4% of long-term lithium users develop grade 3 chronic kidney disease (eGFR <60 ml/min/1.73 m²) compared to 13.1% in control groups 3
• End-stage renal disease (ESRD) is rare, affecting approximately 1% of patients who have taken lithium for over 15 years 3
• The risk of developing CKD significantly increases with longer duration of lithium exposure 2

Types of Renal Damage

Lithium can cause several types of renal complications:

• Nephrogenic diabetes insipidus (NDI): Occurs in approximately 20% of patients on long-term lithium treatment, resulting in polyuria and polydipsia 4
• Progressive renal failure: Occurs in about 20% of long-term lithium users 4
• Interstitial nephritis: Can develop in some patients, potentially leading to severe renal insufficiency 4
• Morphologic changes: Glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy 5

Risk Factors for Renal Damage

• Duration of treatment: Longer exposure to lithium significantly increases risk of renal impairment 2
• Concomitant medications: Combined use of lithium with other psychotropic drugs or medications for somatic disorders increases risk of kidney damage 6
• Episodes of lithium toxicity: Previous lithium intoxication episodes increase risk of renal damage 6
• Dehydration: Inadequate hydration, especially during illness, can precipitate lithium toxicity and renal damage 7
• Medication interactions: Concomitant use of NSAIDs can increase lithium levels and risk of toxicity 7

Monitoring Recommendations

The KDIGO guidelines and other authorities recommend:

• Regular monitoring of renal function: All patients taking potentially nephrotoxic agents such as lithium should have their GFR, electrolytes, and drug levels regularly monitored 8
• Temporary discontinuation: Consider temporary discontinuation of lithium in people with GFR <60 ml/min/1.73 m² who have serious intercurrent illness that increases risk of acute kidney injury 8
• Frequency of monitoring: During initial treatment, lithium levels should be measured twice per week until stabilized 7
• Long-term monitoring: Regular assessment of serum creatinine levels at least yearly 4
• Consultation threshold: Discussion with a nephrologist if creatinine clearance decreases below 60 ml/min 4

Clinical Implications and Management

• Early signs of lithium-related renal toxicity include tremor, nausea, diarrhea, polyuria, and polydipsia 7
• If nephrogenic diabetes insipidus develops, it may initially be reversible if lithium is stopped promptly, but can become permanent over time 4
• For patients who develop significant renal impairment, consider alternative mood stabilizers after consultation with nephrology 4
• Maintain adequate hydration, especially during illness, to prevent lithium toxicity 7

Common Pitfalls and Caveats

• Renal function decline may begin early in treatment, with yearly increases in median serum creatinine levels observed from the first year of lithium treatment 1
• The relationship between renal functional and morphologic changes and their association with lithium therapy has not been definitively established 5
• Lithium toxicity can occur at doses close to therapeutic levels, highlighting the importance of regular monitoring 5
• Patients may not report symptoms of polyuria and polydipsia, making regular laboratory monitoring essential 4

By understanding the incidence and progression of lithium-induced renal damage, clinicians can implement appropriate monitoring strategies to minimize risk while maintaining the therapeutic benefits of lithium therapy.