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.