Supplementary Material for: Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study

<b><i>Background:</i></b> Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. <b><i>Aims:</i></b> We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. <b><i>Methods:</i></b> INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR &lt;60 mL/min/1.73 m². Multivariable conditional logistic regression was used to determine the association of renal function with stroke. <b><i>Results:</i></b> Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m². The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, <i>p</i> &lt; 0.001) and differed by region (<i>p</i> &lt; 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24–1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35–1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17–1.42) (<i>p</i>_interaction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (<i>p</i>_interaction &lt; 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50–3.54 for death within 1 month). <b><i>Conclusion:</i></b> Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.

**背景：** 既往研究已报道肾功能损害与脑卒中存在关联，但该关联的内在机制仍存在不确定性。
**目的：** 本研究旨在探讨该关联是否由共同的危险因素所介导，亦或是独立存在的关联，同时分析该关联是否存在地域差异或脑卒中亚型差异。
**方法：** INTERSTROKE是一项病例对照研究（case-control study），亦是目前规模最大的针对首次急性脑卒中危险因素的国际性研究，共在27个国家完成数据收集。本研究纳入了具备完整血清肌酐（serum creatinine）检测数据的受试者，并计算得到其估算肾小球滤过率（estimated glomerular filtration rate，eGFR）。本研究将肾功能损害定义为eGFR＜60 mL/min/1.73 m²。采用多变量条件logistic回归分析，探讨肾功能水平与脑卒中的关联。
**结果：** 本研究共纳入21127名受试者，其中女性占比41.0%，平均年龄为62.3±13.4岁，平均eGFR为79.9±23.5 mL/min/1.73 m²。病例组肾功能损害患病率显著高于对照组（22.9% vs. 17.7%，p＜0.001），且不同地域间的患病率存在显著差异（p＜0.001）。经校正后，较低的eGFR与脑卒中发生风险升高显著相关。肾功能损害与全脑卒中风险升高相关（比值比（odds ratio，OR）=1.35，95%置信区间（confidence interval，CI）：1.24~1.47），其中脑出血（intracerebral hemorrhage）患者的关联强度（OR=1.60，95%CI：1.35~1.89）高于缺血性脑卒中（ischemic stroke）患者（OR=1.29，95%CI：1.17~1.42）（交互作用p=0.12）。该关联在年轻受试者以及居住在非洲、南亚或南美洲的人群中最为显著（全脑卒中的交互作用p＜0.001）。此外，肾功能损害还与较差的临床预后相关（1个月内死亡的相对风险比（relative risk ratio，RRR）=2.97，95%CI：2.50~3.54）。
**结论：** 肾功能损害是脑卒中的重要危险因素，尤其在年轻患者中更为突出，且与病情更严重的脑卒中及不良临床预后密切相关。