Chronic kidney disease associated with an increased risk of spontaneous intracranial hemorrhage

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1. Chronic renal failure was independently associated with an increased risk of spontaneous intracranial hemorrhage, regardless of race or ethnicity.

2. Genetically determined chronic renal failure was also associated with an increased risk of intracranial hemorrhage.

Assessment of the level of proof: 2 (good)

Summary of the study: Spontaneous, non-traumatic intracranial hemorrhage can be a devastating event that is often secondary to hypertension, vascular aneurysms, or other cerebral vessel malformations. Previous studies have suggested an increased risk of ischemic stroke in people with chronic kidney disease (CKD), but the relationship between CKD and hemorrhagic stroke is less clear. The present study by Vanent et al combined observational and genetic data from a large cohort of individuals to assess the association between CKD and spontaneous, non-traumatic intracranial hemorrhage (ICH).

A total of 6,868 patients from the ERICH case-control study were included. The prevalence of CKD among cases was 4.3% and 1.3% among controls; This difference was statistically significant. Among the general population cohort of 502,536 people, 1,341 patients with ICH were identified. The prevalence of CKD in patients with ICH was 6.4% and 1.9% in non-ICH controls. Finally, 1,078 cases of CKD of genetic origin were identified, which were also associated with an increased risk of ICH. The analysis of the functional results 3 months after the intracranial hemorrhage demonstrated that patients with CKD had poorer results.

This observational study by Vanent et al demonstrated that people with CKD are at an increased risk of dangerous cerebral hemorrhagic events and also an increased risk of poor functioning following ICH. These results are significant as they provide early rationale for screening for hypertension and associated intracranial pathologies in patients with CKD. A strength of this study is the large sample size as well as the plausibility of the results reported based on previous studies in this area. However, a main limitation of this work is the potential for confounding: for example, patients with CKD are known to be relatively comorbid, which may further influence the risk of ICH. Given this, further research is needed to better understand the mechanism underlying the association described in this study.

Click here to read this study in JAMA Neurology

Relevant reading: Chronic Kidney Disease and Stroke Risk: A Systematic Review and Meta-Analysis

In depth [retrospective cohort]: A multi-stage study was conducted. Observational data from the ERICH case-control study on patients with CKD were collected retrospectively to assess any association between CKD and ICH. This same analysis was then repeated in an ethnically diverse cohort drawn from the general population. Finally, a Mendelian randomization genetic analysis was performed among this larger cohort to determine which CKD patients had inherited the disease and whether this affected its relationship to ICH risk. Eligible patients in all phases of this study were adults living within 75 miles of a study enrollment center. Cases in the ERICH study had an image-confirmed diagnosis of ICH. Genetic analysis was performed using standard methods.

Analysis of the ERICH cohort confirmed that CKD was associated with an increased risk of ICH: in unadjusted analyzes (odds ratio [OR], 3.35; 95% CI, 2.33-4.82) and adjusted analyzes (OR, 1.95; 95% CI, 1.35-2.89). End-stage renal disease was associated with a higher risk of ICH: in unadjusted analyzes (OR, 5.44; 95% CI, 2.85-10.37) and adjusted analyzes (OR, 2. 93; 95% CI, 1.51-5.67). Analysis of patients in the general population demonstrated that CKD was also associated with an increased risk of ICH: in unadjusted analyzes (OR, 3.60; 95% CI, 2.89-4.48 ) and adjusted analyzes (OR 1.28; 95% CI, 1.01-1.62).

Genetic CKD was associated with an increased likelihood of ICH even using a conservative analytical approach (weighted mean) yielding an odds ratio of 1.72 (95% confidence interval 1.06-2.82 ). The risk of poor functional outcome 3 months after an intracranial haemorrhage was increased in people with CKD (58.8%) compared to those without CKD (47.9%), p = 0.003. This association was not modified by race or ethnicity data.

Picture: PD

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