RESUMO
BACKGROUND: Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. METHODS: Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8-48 (mean 18) years and aged 20-89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea-nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. RESULTS: Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years. LIMITATIONS: Control data for age-matched subjects not exposed to lithium were lacking. CONCLUSIONS: Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.
RESUMO
OBJECTIVES: We assessed kidney function in long-term lithium-treated bipolar patients compared with age-matched patients not taking lithium, including novel markers of kidney injury such as plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta-2 microglobulin (ß2-MG) METHODS: The study comprised 120 patients with bipolar disorder of which 90 (30 males and 60 females) have been receiving lithium for 5-38 (mean 16) years, and 30 (10 males and 20 females) have never been exposed to lithium. RESULTS: Lithium-treated patients, both men and women, showed significantly higher plasma NGAL and urinary ß2-MG and lower urine specific gravity and estimated glomerular filtration rate (eGFR), compared with patients not taking lithium. In these patients, serum NGAL did not correlate with any clinical feature or other parameter of kidney function. Urinary ß2-MG correlated with serum creatinine and eGFR in the whole group of lithium-treated patients and in addition, in males, with duration of illness, duration of lithium treatment, and urine specific gravity. CONCLUSIONS: Lithium treatment causes an impairment of kidney function reflected also by abnormal levels of novel markers of kidney injury. Of these, urinary ß2-MG, as a marker of tubular function seems to be better predictor than serum NGAL in lithium-treated patients because it shows multiple clinical and biochemical correlations, especially in men.