Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria

Introduction

Lithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output.

Methods

Prospective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in n = 119), and measured glomerular filtration rate (mGFR). Maximal urine osmolality (MaxUosm) was the highest level during the DDAVP test.

Results

Of the individuals, 21% displayed polyuria (>3 l/d), but 55% displayed elevated fasting vasopressin level (>5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for >10 years. MaxUosm was >600 mOsm/KgH₂O in 128 patients (59%), among which vasopressin was increased in 51%, associated with higher lithium dose (950 [750–1200] vs. 800 [500–1000] mg/d, P < 0.001). All patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (β 0.49 ± 0.17, P = 0.005), female sex (β −359 ± 123, P = 0.004), daily osmolar intake (β 2.21 ± 0.24, P < 0.001), MaxUosm (β −2.89 ± 0.35, P < 0.001), and plasma vasopressin level (β 10.17 ± 4.76, P = 0.03).

Conclusion

Higher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.