Is Chronic Kidney Disease Associated With Intracerebral Hemorrhage Risk?

Chronic kidney disease (CKD) is independently associated with an increased risk for spontaneous intracerebral hemorrhage (ICH), regardless of race or ethnicity. Moreover, inherited CKD is also associated with increased ICH risk. These are the findings of an observational analysis published in JAMA Neurology.

Spontaneous ICH is associated with a high mortality rate and fewer than 30% of patients regain the mobility following an ICH event. Previous research has suggested that CKD is associated with increased risk for ICH. To more robustly evaluate the relationship between CKD and ICH, researchers at Yale School of Medicine conducted a 3-stage study that combined observational and genetic data from 2 large cohorts of individuals.

First, the association between CKD and ICH risk was evaluated using data from the multicenter case-control Ethnic/Racial Variations of Intracerebral Hemorrhage study (ERICH; Clinicaltrials.gov Identifier: NCT01202864), which enrolled 2914 participants with ICH and 2954 control individuals. The study was conducted between August 1, 2010 to August 1, 2017 and researchers observed participants for 1 year.

Then, the findings from the ERICH analysis were confirmed using independent data from over 500,000 individuals enrolled in the UK Biobank, an ongoing population study in the UK, between 2006 and 2010.

In the third stage, a Mendelian analysis was performed in the UK Biobank cohort to identify which patients with CKD had inherited disease, and whether this impacted ICH risk. The researchers also performed a separate analysis of CKD and functional outcome after ICH in ERICH.

The ERICH and UK Biobank cohorts comprised individuals aged mean 56.5-61.6 years, 41.5%-54.4% were women, 33.6%-94.2% were White, 5.6%-68.5% had individual vascular risk factors, and 2.0%-69.2% had individual comorbidities.

In the ERICH analysis, CKD was associated with increased risk for ICH after adjusting for cofactors (adjusted odds ratio [aOR], 1.95; 95% CI, 1.35-2.89; P <.001), which was confirmed in the sensitivity analysis (aOR, 2.93; 95% CI, 1.51-5.67; P <.001). Similarly, CKD associated with increased ICH risk in the UKBiobank sample (aOR, 1.28; 95% CI, 1.01-1.62; P =.04). In the MR analysis, genetically determined CKD was associated with ICH risk using both the inverse variance-weighted (OR, 1.56; 95% CI, 1.13-2.16; P =.007) and weighted-median (OR, 1.72; 95% CI, 1.06-2.82; P =.03) approaches. No evidence of horizontal pleiotropy was observed.

In the sensitivity analysis, CKD was also associated with hypertension and diabetes (OR, 1.57; 95% CI, 1.12-2.19; P =.008).

In the separate analysis, at 3 months following ICH, CKD was associated with poorer functional outcomes compared with patients who did not have CKD (OR, 2.05; 95% CI, 1.13-3.07; P <.001). This relationship was modified by ICH location, in which CKD increased risk for poorer functional outcomes following lobar ICH (OR, 4.03; 95% CI, 1.69-10.12; P =.002) compared with nonlobar ICH (OR, 1.74; 95% CI, 1.10-2.76; P =.02). However, race and ethnicity did not modify this association.

The researchers stated that “Although our study provides important evidence to support a causal association between CKD and ICH, the pathways mediating this association remain to be identified.”

They concluded, “Future research is needed to elucidate the biologic mechanisms responsible for the associations of CKD with the risk and severity of ICH and to study the genetic associations reported here in Asian, Black, and Hispanic or Latino populations.”

This study may have been limited by combining two independent cohorts with differing inclusion and exclusion criteria, resulting in a heterogeneous study population.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.