炭酸リチウム誘発性腎機能障害の発症予測因子の解析：多施設後ろ向きコホート研究

抄録

Lithium carbonate is one of the first-line pharmacological treatments for mania and bipolar disorder, and its efficacy has been demonstrated in placebo-controlled trials. However, lithium is associated with adverse effects, including renal impairment, which can elevate serum lithium levels and increase toxicity risk. Although factors such as age, sex, comorbidities, dosage, and co-medications may influence renal impairment, previous findings have been inconsistent. This multicenter, retrospective cohort study aimed to identify risk factors for the onset and progression of lithium-induced renal impairment. Patients who initiated lithium therapy between April 2001 and December 2020 at participating institutions were included. Individuals with preexisting renal dysfunction, insufficient baseline data, or missing follow-up renal measurements were excluded. Renal function was assessed using the estimated glomerular filtration rate (eGFR) at six predefined time windows within two years after treatment initiation. The primary outcome was the development of renal impairment (eGFR < 60 mL/min/1.73m²) within 2 years. Among the 183 patients analyzed, 26 (14.2％) developed renal impairment. Mixed-effects logistic regression revealed that older age, lower pre-treatment eGFR, longer treatment duration, and a dosing frequency of two or more times per day were significantly associated with increased odds of renal impairment. In contrast, the daily lithium dose was not significantly associated with renal function decline. These findings indicate that lithium-induced renal impairment is more likely to occur with increasing age, longer treatment duration, and higher dosing frequency. Once-daily dosing may help reduce the risk, and regular renal monitoring is recommended, particularly in high-risk patients receiving long-term lithium therapy.