Does Lithium Increase Urine Output?
Yes, lithium significantly increases urine output in a substantial proportion of patients, with polyuria (>3 L/day) occurring in approximately 21% of lithium-treated individuals and elevated urine volumes affecting up to 85% of patients on long-term therapy. 1, 2, 3
Mechanism and Clinical Presentation
Lithium causes nephrogenic diabetes insipidus by decreasing sodium reabsorption in the renal tubules, which leads to impaired urinary concentrating ability. 1 The FDA drug label explicitly states that "polyuria and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment," and warns that patients may develop "thirst or polyuria, sometimes resembling diabetes insipidus." 1
- Early signs of toxicity include polyuria-polydipsia along with tremor, nausea, and diarrhea, which can occur even at therapeutic lithium levels. 4, 1
- The mechanism involves lithium's effect on vasopressin resistance at the collecting duct level, with 55% of lithium-treated patients displaying elevated fasting vasopressin levels (>5 pg/ml) despite increased urine output. 2
Risk Factors for Increased Urine Output
Duration of lithium therapy is the most important risk factor for developing polyuria and tubular dysfunction. 5
- Patients treated for >10 years show significantly lower urine osmolality and higher urinary output compared to those with shorter treatment duration. 2
- Higher lithium daily doses are independently associated with higher urine output (β 0.49 ± 0.17, P = 0.005) and elevated vasopressin levels. 2
- All patients receiving lithium doses ≥1400 mg/day had elevated vasopressin levels in one study. 2
- Female sex is associated with lower 24-hour urine output (β -359 ± 123, P = 0.004). 2
Dosing Schedule Impact
Once-daily dosing at night appears less harmful to renal function than divided doses throughout the day. 6, 7, 3
- Patients receiving lithium in a single daily dose (given between 8-10 PM) had significantly lower urinary output than those on multiple-dosage schedules. 6, 7
- The structural and functional kidney changes were most pronounced in patients given divided doses during the day. 6
- This protective effect may occur because regenerative processes only function during periods with low lithium concentrations. 6
- Discontinuity in lithium treatment minimizes effects on kidney function. 3
Clinical Management Considerations
Baseline and ongoing monitoring are essential given lithium's renal effects. 8, 4
- The American Academy of Child and Adolescent Psychiatry recommends baseline urinalysis, blood urea nitrogen, and creatinine before starting lithium. 8, 4
- Renal function tests and urinalysis should be monitored every 3-6 months once stable. 8, 4
- Monitoring frequency should increase during intercurrent illness. 4
Patients must maintain adequate hydration and salt intake to prevent sodium depletion. 1
- The FDA label recommends maintaining normal diet including salt and adequate fluid intake (2500-3000 mL) at least during initial stabilization. 1
- Decreased tolerance to lithium occurs with protracted sweating or diarrhea, requiring supplemental fluid and salt. 1
Medication Interactions Affecting Renal Function
NSAIDs should be avoided in lithium-treated patients as they are contraindicated. 8
- Diuretics and ACE inhibitors used concomitantly with lithium may reduce renal clearance and increase lithium toxicity risk. 1
- Lithium should be temporarily discontinued during serious intercurrent illness that increases AKI risk in patients with GFR <60 ml/min/1.73 m². 8
Strategies to Reduce Polyuria
Controlled salt and protein intake along with optimized lithium dosing may reduce polyuria. 2