Ercis Mete, Tarikogullari Idil, Pazdernik Vanessa K, Gonzalez-Suarez Maria L, Baweja Raman, Miola Alessandro, Abulseoud Osama A, Leung Jonathan G, McElroy Susan L, Cuellar-Barboza Alfredo B, Gitlin Michael J, Ozerdem Aysegul, Frye Mark A, Singh Balwinder
Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
medRxiv. 2025 Sep 3:2025.09.02.25334914. doi: 10.1101/2025.09.02.25334914.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed for type 2 diabetes, have shown promise in improving renal outcomes in patients with and without diabetes. However, their effect on lithium-associated kidney dysfunction remains unknown.
This historical cohort study included patients from Mayo Clinic (2001-2023) with mood disorders who received lithium for ≥6 months and later used SGLT2i for ≥1 month. Data on SGLT2i use and lithium treatment were extracted from electronic health records. Serum creatinine values were used to calculate estimated glomerular filtration rate (eGFR) trajectories. Linear mixed-effects models with piecewise linear splines were used to estimate eGFR slopes before and after SGLT2i initiation, adjusted for age and sex.
Fifty-six patients (mean age 57.4 years, 46.4% female), predominantly with bipolar disorder (86%), were included. The mean eGFR, measured nearest to SGLT2i initiation, was 77.9±26.0 mL/min/1.73 m, and the mean duration of SGLT2i use was 19.5±17.8 months. Before SGLT2i initiation, eGFR declined at a rate of -1.43 mL/min/1.73 m per year (p<0.001). After initiation, eGFR increased by 0.69 mL/min/1.73 m per year, reflecting a +2.13 change (p=0.025). Sensitivity analyses, including only patients on lithium at SGLT2i initiation (n=22) or who had >1 year of SGLT2i use (n=29) showed similar, though non-significant, changes in slopes.
SGLT2i treatment was associated with a significant improvement in eGFR trajectory in patients with mood disorders who received long-term lithium therapy. These findings suggest a potential role for SGLT2is in mitigating lithium-associated kidney dysfunction and highlight the need for randomized controlled trials in this population.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）最初是为2型糖尿病开发的，已显示出有望改善糖尿病患者和非糖尿病患者的肾脏结局。然而，它们对锂相关肾功能障碍的影响尚不清楚。
这项历史性队列研究纳入了梅奥诊所（2001年至2023年）患有情绪障碍且接受锂治疗≥6个月并随后使用SGLT2i≥1个月的患者。从电子健康记录中提取SGLT2i使用和锂治疗的数据。血清肌酐值用于计算估计肾小球滤过率（eGFR）轨迹。使用带有分段线性样条的线性混合效应模型来估计SGLT2i开始使用前后的eGFR斜率，并根据年龄和性别进行调整。
纳入了56名患者（平均年龄57.4岁，46.4%为女性），主要患有双相情感障碍（86%）。在最接近SGLT2i开始使用时测量的平均eGFR为77.9±26.0 mL/min/1.73 m²，SGLT2i的平均使用时长为19.5±17.8个月。在SGLT2i开始使用前，eGFR以每年-1.43 mL/min/1.73 m²的速度下降（p<0.001）。开始使用后，eGFR每年增加0.69 mL/min/1.73 m²，反映出+2.13的变化（p=0.025）。敏感性分析，包括仅在SGLT2i开始使用时正在服用锂的患者（n=22）或使用SGLT2i超过1年的患者（n=29），显示斜率有相似但不显著的变化。
SGLT2i治疗与接受长期锂治疗的情绪障碍患者的eGFR轨迹显著改善相关。这些发现表明SGLT2i在减轻锂相关肾功能障碍方面具有潜在作用，并强调了在该人群中进行随机对照试验的必要性。
