Acute ischemic stroke (AIS) is the second leading cause of death worldwide after coronary heart disease. Acute kidney injury (AKI) is one serious complication after AIS, and homocysteine (Hcy) may be an important factor associated with kidney injury and accelerated deterioration of renal function. However, there are few studies on the relationship between Hcy and AKI, especially in patients with AIS.

To investigate the relationship between plasma Hcy level and AKI in patients with AIS, and to provide new ideas for the prevention and treatment of AKI.

Baseline clinical data of 1 202 patients with AIS who were admitted to Department of Neurology, the Second Hospital of Tianjin Medical University were collected from the electronic medical record systemfrom January 2018 to April 2021. Patients were divided into normal Hcy (Hcy≤15 μmol/L, n=618), mild hyperhomocysteinemia (HHcy) (16 μmol/L<Hcy≤30 μmol/L, n=459) and moderate-to-severe HHcy (Hcy>30 μmol/L, n=125) groups according to the Expert Consensus on the Diagnosis, Treatment, and Prevention of Hyperhomocysteinemia. Patients were divided into AKI group and non-AKI group by the values of ambulatorily monitored renal function and urine volume within seven days after admission recommended in the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Multivariate Logistic regression was used to explore the effects of Hcy on post-AIS AKI as a continuous variable and a categorical variable, respectively. Subgroup analysis was used to investigate the relationship between Hcy and AKI in subgroups. The nonlinear relation between Hcy and AKI was explored by restricted cubic spline regression.

One hundred and fifty patients (12.48%) developed AKI in all subjects. Multivariate Logistic regression showed that after adjustment for potential confounders, the risk of AKI increased by 1.035 times〔OR=1.035, 95%CI (1.019, 1.052), P<0.05〕 for every 1 μmol/L increase in Hcy. With reference to normal Hcy, mild and moderate-to-severe HHcy has been associated with a 1.770-fold〔OR=1.770, 95%CI (1.150, 2.724), P<0.05〕 and 2.927-fold 〔OR=2.927, 95%CI (1.671, 5.126), P<0.05〕 increased risk of AKI, separately. Subgroup analysis found that the risk of AKI after AIS increased with the increase of Hcy level (used as a continuous variable) in females, those aged ≥75 years, those with hypertension, diabetes or moderate to severe stroke at admission, and those whose stroke type was large-artery atherosclerosis (LAA), small artery occlusion (SAO) or cardio embolism (CE) (P<0.05). When Hcy was analyzed as a categorical variable, mild HHcy was associated with a higher risk of AKI compared with normal Hcy in the male population, those aged<75 years, those with hypertension, diabetes, a history of stroke or mild stroke at admission, and those without coronary heart disease (P<0.05). And moderate-to-severe HHcy was associated with a higher risk of AKI compared with normal Hcy in the female population, those with hypertension, diabetes, or moderate or moderate-to-severe stroke at admission, and those whose stroke type was LAA, SAO or CE regardless of age, coronary heart disease and history of stroke (P<0.05). Restricted cubic regression manifested that there was a nonlinear correlation between Hcy and the risk of AKI, and the curve was convex (P=0.026). The risk of AKI after AIS increased rapidly with the increase of Hcy when admission Hcy was less than 17 mmol/L, but increased slowly with the increase of Hcy when admission Hcy was greater than or equal to 17 mmol/L.

Elevated Hcy is a risk factor for AKI whether as a continuous variable or a categorical variable in AIS patients. So monitoring the level of Hcy is conducive to early identification and prevention of AKI, which is helpful to improve the prognosis in AIS patients.

急性缺血性脑卒中（AIS）是全球范围内仅次于冠心病的第二大死亡原因，急性肾损伤（AKI）是AIS后较为严重的并发症之一，同型半胱氨酸（Hcy）可能是导致肾损伤和加速肾功能恶化的重要因素。然而目前AIS患者中关于Hcy与AKI关系的研究尚少。

探讨AIS患者Hcy水平与AKI的发生关系，为AIS患者AKI的防治提供更多思路。

纳入2018年1月—2021年4月天津医科大学第二医院神经内科收治的住院AIS患者1 202例为研究对象，通过院内电子病历系统收集基线临床资料。依据《高同型半胱氨酸血症的诊断、治疗与预防专家共识》将患者分为3类：Hcy正常者（Hcy≤15 μmol/L，n=618）、轻型高同型半胱氨酸血症（HHcy）者（Hcy为16~30 μmol/L，n=459）及中重型HHcy者（Hcy>30 μmol/L，n=125）。动态监测患者入院7 d内肾功能和尿量变化，参照2021年改善全球肾脏病预后指南的AKI诊断标准，根据患者是否发生AKI分为AKI组和非AKI组。采用多因素Logistic回归分析探究Hcy分别作为连续变量与分类变量对AIS后发生AKI的影响。采用亚组分析探讨各亚组人群中Hcy与AIS后发生AKI的关系，采用限制性立方样条模型探究Hcy与AIS后发生AKI的非线性关系。

1 202例AIS患者中150例（12.48%）发生AKI（AKI组）。多因素Logistic回归分析结果显示，调整混杂变量后Hcy每升高1 μmol/L，AIS后发生AKI的风险增加〔OR=1.035，95%CI（1.019，1.052），P<0.05〕；以Hcy正常者为参照组，轻型和中重型HHcy者发生AKI的风险均增加〔OR=1.770，95%CI（1.150，2.724），P<0.05；OR=2.927，95%CI（1.671，5.126），P<0.05〕。亚组分析结果显示，Hcy作为连续变量时，在女性、年龄≥75岁、有高血压、有糖尿病、有无脑卒中病史、入院时为中重度脑卒中及脑卒中类型为大动脉粥样硬化型（LAA）、小动脉闭塞型（SAA）或心源性栓塞型（CE）的AIS患者中，AKI的发生风险随Hcy水平的升高而增加（P<0.05）。Hcy作为分类变量时，在男性、<75岁、有高血压、有糖尿病、有脑卒中病史、无冠心病及入院时为轻度脑卒中的AIS患者中，轻型HHcy者较Hcy正常者发生AKI的风险升高（P<0.05）。在女性、有高血压、有糖尿病、无论年龄大小、是否有冠心病、是否有脑卒中病史、入院时为中度或中重度脑卒中及脑卒中类型为LAA、SAA或CE的AIS患者中，中重型HHcy者较Hcy正常者发生AKI的风险升高（P<0.05）。限制性立方样条模型结果显示，Hcy与AKI发生风险之间存在非线性关联，且呈上凸型曲线（P=0.026）。当入院时Hcy<17 mmol/L时，AIS后发生AKI的风险随Hcy的升高快速升高；当入院时Hcy≥17 mmol/L时，AIS后发生AKI的风险随Hcy的升高而缓慢上升。

Hcy无论作为连续变量还是分类变量均是影响AIS后发生AKI的危险因素，监测患者Hcy水平有助于早期识别并预防AKI，改善患者预后。