There are limited studies regarding the safety of methotrexate (MTX) in patients with reduced renal function. This study aimed to investigate methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA) and renal dysfunction. This retrospective cohort study included patients with RA and renal dysfunction. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m². We classified the patients into two groups according to the onset of renal dysfunction: newly and previously developed group. MTX-associated toxicity included renal toxicity, hepatotoxicity, serious infection, pancytopenia, leukopenia, thrombocytopenia and mucositis. Cox analysis was performed to determine the factors associated with toxicity. The study included 120 patients with RA and renal dysfunction receiving MTX (66: newly developed; 54: previously developed). The median eGFR was 52.1 mL/min/1.73 m² [IQR 47.1–57.3]. Thirty-five patients (29.2%) experienced toxicity, and the median time to toxicity events was 23 months (IQR 10–57). Toxicity was distributed as follows: leukopenia (10%, 12/120), renal toxicity (5.8%, 7/120), hepatotoxicity (7.5%, 9/120), serious infection (8.3%, 10/120), pancytopenia (5.0%, 6/120), thrombocytopenia (5.8%, 7/120), and mucositis (5.8%, 7/120). The toxicity rate did not differ significantly between newly and previously developed group [23/66 (34.8%) vs. 12/54 (22.2%), P = 0.130]. Multivariate analysis revealed that hydroxychloroquine use (HR 0.425, 95% CI 0.212–0.853, P = 0.016), baseline eGFR (HR 0.938, 95% CI 0.890–0.988, P = 0.015) and being female (HR 10.538, 95% CI 1.375–80.793, P = 0.023) were associated with MTX-related toxicity. Toxicity occurred in approximately 30% of patients with RA and renal dysfunction receiving MTX treatment. Hydroxychloroquine use exhibited a protective effect against MTX-associated toxicity development.

关于甲氨蝶呤（MTX）在肾功能不全患者中的安全性研究有限。本研究旨在研究类风湿关节炎（RA）和肾功能不全患者的甲氨蝶呤（MTX）相关毒性。这项回顾性队列研究包括RA和肾功能不全的患者。肾功能不全定义为估计的肾小球滤过率（eGFR）<60 mL / min / 1.73 m ²。我们根据肾功能不全的发作将患者分为两组：新组和先前组。与MTX相关的毒性包括肾毒性，肝毒性，严重感染，全血细胞减少，白细胞减少，血小板减少和粘膜炎。进行Cox分析以确定与毒性相关的因素。该研究纳入了接受MTX治疗的120例RA和肾功能不全患者（66例：新开发的； 54例：先前开发的）。eGFR中位数为52.1 mL / min / 1.73 m ²[IQR 47.1-57.3]。三十五名患者（29.2％）经历了毒性反应，中毒发生时间的中位数为23个月（IQR 10-57）。毒性分布如下：白细胞减少症（10％，12/120），肾毒性（5.8％，7/120），肝毒性（7.5％，9/120），严重感染（8.3％，10/120），全血细胞减少（ 5.0％，6/120），血小板减少症（5.8％，7/120）和粘膜炎（5.8％，7/120）。新组和先前组之间的毒性率没有显着差异[23/66（34.8％）与12/54（22.2％），P  = 0.130]。多变量分析显示，使用羟氯喹（HR 0.425，95％CI 0.212-0.853，P  = 0.016），基线eGFR（HR 0.938，95％CI 0.890-0.988，P  = 0.015）和女性（HR 10.538，95％CI 1.375） –80.793，P = 0.023）与MTX相关的毒性有关。接受MTX治疗的RA和肾功能不全患者中约有30％发生了毒性反应。羟氯喹的使用对MTX相关的毒性发展具有保护作用。