Tondo Leonardo, Abramowicz Maria, Alda Martin, Bauer Michael, Bocchetta Alberto, Bolzani Lorenza, Calkin Cynthia V, Chillotti Caterina, Hidalgo-Mazzei Diego, Manchia Mirko, Müller-Oerlinghausen Bruno, Murru Andrea, Perugi Giulio, Pinna Marco, Quaranta Giuseppe, Reginaldi Daniela, Reif Andreas, Ritter Philipp, Rybakowski Janusz K, Saiger David, Sani Gabriele, Selle Valerio, Stamm Thomas, Vázquez Gustavo H, Veeh Julia, Vieta Eduard, Baldessarini Ross J
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
The International Consortium for Mood & Psychotic Disorders Research, MRC 306, McLean Hospital, 115 Mill Street, Belmont, MA, 02478-9106, USA.
Int J Bipolar Disord. 2017 Dec;5(1):27. doi: 10.1186/s40345-017-0096-2. Epub 2017 Aug 1.
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.
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.
Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m), 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/m. 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.
Control data for age-matched subjects not exposed to lithium were lacking.
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.
长期将锂作为一种情绪稳定药物进行治疗，人们对其潜在的不良反应尤为关注，其中显著包括肾功能改变。然而，严重肾功能不全的发生率、随时间的下降速率、锂剂量、血清浓度和治疗持续时间的影响、锂暴露与衰老的相对影响以及性别和其他因素的作用均尚不清楚。
因此，我们从12个国际合作研究点收集了数据，涉及312例双相情感障碍患者（6142人年，2669次检测），这些患者接受碳酸锂治疗8 - 48年（平均18年），年龄在20 - 89岁（平均56岁）。我们评估了估算肾小球滤过率（eGFR）以及血清肌酐、尿素氮、葡萄糖浓度、白细胞计数和体重指数的变化，并使用标准双变量对比和回归模型测试了eGFR与选定因素之间的关联。
总体而言，29.5%的受试者至少有一次eGFR低值（<60 mL/min/1.73 m²），大多数出现在治疗≥15年后且年龄>55岁时；eGFR≥2次低值的风险为18.1%；无人发生终末期肾衰竭。eGFR每年随年龄下降0.71%，随治疗时间下降0.92%，女性下降幅度比男性高19%。平均血清肌酐从0.87 mg/dL增至1.17 mg/dL，尿素氮从23.7 mg/dL增至33.1 mg/dL，葡萄糖从88 mg/dL增至122 mg/dL，体重指数从25.9 kg/m²增至26.6 kg/m²。通过多变量回归分析，eGFR下降的风险因素排序为：锂治疗时间更长、锂剂量更低、血清锂浓度更高、年龄更大以及合并其他疾病。初始eGFR较低以及≥40岁开始使用锂治疗也预示着后期会出现eGFR低值。
缺乏未接触锂的年龄匹配受试者的对照数据。
长期锂治疗与肾功能（eGFR）逐渐下降相关，其下降幅度比仅与衰老相关的下降幅度高约30%。eGFR低于正常水平的风险为18.1%（≥2次低值）至29.5%（≥1次低值），这需要约30年的暴露时间。eGFR低值的其他风险因素包括血清锂水平较高、锂治疗时间更长、初始eGFR较低、合并其他疾病以及年龄较大。
