Chronic kidney disease (CKD), defined as either a reduced kidney function based on estimated glomerular filtration rate (eGFR) and cystatin C (CysC) or the presence of kidney damage, is associated with an increased risk for intracranial atherosclerotic disease (ICAD), according to study results published in Neurology.

Previous studies have reported an increased risk for cardiovascular morbidity and mortality among patients with CKD, but limited data are available on the association between CKD and ICAD and whether the association between CKD and extracranial atherosclerosis can be generalized to intracranial arteries. The goal of the current study was to explore the association between reduced kidney function and kidney damage with ICAD.

The researchers used data from the Atherosclerosis Risk in Communities (ARIC) study and included data on kidney function measurements and 3-dimensional vessel wall MRI. This technique is able to characterize intracranial plaques as well as the severity of stenosis and serves as an effective tool for assessing ICAD.

The associations between kidney measures and ICAD status were analyzed in binomial (presence vs absence of ICAD, presence vs absence of detectable stenosis) and multinomial (0 vs 1 and 0 vs ≥2 plaques, absent or mild stenosis vs 50%−70% and >70% stenosis or occlusion). The main outcomes were presence of intracranial plaques and luminal stenosis.


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The analysis included 1762 participants (mean age 76.3 years, 41.5% men) who received MRI scans with good vessel wall image quality and with available kidney measures. Most patients (63.7%) did not have a plaque on vessel wall MRI; 293 (16.6%) had 1 plaque; and 347 (19.7%) had multiple (≥2) plaques. Among 640 participants with at least 1 plaque, 189 (29.5%) had ≥1 plaque causing ≥50% stenosis, and 944 (14.7%) had ≥1 plaque causing >70% stenosis or occlusion.

A total of 51.7% of participants with plaques and 42.2% of those without plaques had eGFR based on CysC (eGFRcysc) <60 mL/min/1.73 m2. The risk for ICAD was significantly increased for patients with reduced kidney function, compared to those with normal kidney function (adjusted odds ratio [aOR] 1.29; 95% CI, 1.04-1.60). Furthermore, eGFRcysc <60 mL/min/1.73 m2 was associated with presence of any detectable stenosis (aOR 1.31; 95% CI 1.04-1.63) and with the presence of >70% stenosis or occlusion independently (OR 2.15; 95% CI 1.32-3.50) but not with lesser degrees of stenosis.

In adjusted multinomial logistic regression models, eGFRcysc <60 mL/min/1.73 m2 was associated with a 41% increased risk for having a single plaque (aOR 1.41; 95% CI, 1.06-1.87), compared to no plaque, but there was no significantly increased risk for multiple plaques.

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While elevated albumin-to-creatinine ratio (ACR) or CysC did not show significant associations with plaque presence when assessed as continuous variables, in multinomial logistic regression models, albuminuria was associated with presence of 50% to 70% stenosis with an adjusted OR of 2.01 (95% CI 1.14–3.55) for ACR ≥30 (vs <30) and 2.88 (95% CI 1.03–8.10) for ACR ≥300 (vs <300). CysC was associated with presence of >70% stenosis or occlusion independently (aOR 3.16; 95% CI 1.44–6.94).

The study had several limitations, according to the researchers, including the cross-sectional design, inclusion of relatively healthy, and small number of subjects with significant stenosis.

“Our study revealed that CKD is associated with ICAD in a subset of participants in the ARIC cohort. Thus, kidney disease should be considered an important factor in risk stratification for cerebrovascular disease,” concluded the researchers.

Reference

Hao Q, Gottesman RF, Qiao Y, et al. Association between kidney disease measures and intracranial atherosclerosis: The ARIC study [published online ahead of print, 2020 Apr 17]. Neurology. doi:10.1212/WNL.0000000000009311