Department of Neurology, Yale School of Medicine, New Haven, Connecticut.
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
JAMA Neurol. 2022 Sep 1;79(9):911-918. doi: 10.1001/jamaneurol.2022.2299.
The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.
To determine whether there is an association between CKD and ICH risk.
DESIGN, SETTING, AND PARTICIPANTS: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.
CKD stages 1 to 5.
The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.
In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007).
In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.
由于慢性肾脏病 (CKD) 和自发性脑出血 (ICH) 常同时存在于这两种疾病的患者中，因此可能存在混杂因素，导致这两种疾病之间的关联证据并不明确。
确定 CKD 是否与 ICH 风险相关。
设计、设置和参与者：这是一项包括观察性和遗传分析的 3 期研究。首先，在 ERICH 研究中测试了 CKD 和 ICH 风险之间的关联，这是一项在美国进行的多中心病例对照研究。所有纳入的 ERICH 参与者都有 CKD 相关数据。其次，在 UKB 中对该分析进行了复制，这是一项在英国进行的正在进行的人群研究。UKB 的所有参与者都纳入了本研究。第三，使用 27 个与 CKD 相关的遗传变异进行 UKB 的孟德尔随机化分析，以测试遗传关联。ERICH 于 2010 年 8 月 1 日至 2017 年 8 月 1 日进行，观察参与者 1 年。UKB 于 2006 年至 2010 年期间招募参与者，并将继续观察他们 30 年。数据分析于 2019 年 11 月 11 日至 2022 年 5 月 10 日进行。
CKD 1 至 5 期。
感兴趣的结局是 ICH，在 ERICH 中通过神经图像的专家评估确定，在 UKB 中通过自我报告数据和国际疾病分类，第十次修订，代码的组合确定。
在 ERICH 研究中，共评估了 2914 名 ICH 患者和 2954 名有 CKD 相关数据的对照组参与者（平均[SD]年龄，61.6[14.0]岁；2433 名女性参与者[41.5%]；3435 名男性参与者[58.5%]）；发现 CKD 与更高的 ICH 风险独立相关（比值比[OR]，1.95；95%置信区间[CI]，1.35-2.89；P<0.001）。这种关联不受种族和民族的影响。在 UKB 中对 1341 名 ICH 患者和 501195 名对照组参与者进行的复制（平均[SD]年龄，56.5[8.1]岁；273402 名女性参与者[54.4%]；229134 名男性参与者[45.6%]）证实了这一关联（OR，1.28；95%CI，1.01-1.62；P=0.04）。孟德尔随机化分析表明，遗传决定的 CKD 与 ICH 风险相关（OR，1.56；95%CI，1.13-2.16；P=0.007）。
在这项 3 期研究中，我们对 2 项具有不同特征和研究设计的大型观察性研究中的研究参与者进行了观察性和遗传分析，结果一致表明 CKD 与 ICH 风险增加相关。孟德尔随机化分析表明这种关联是因果关系。需要进一步的研究来确定介导这种关联的具体生物学途径。
