Interplay Between Chronic Kidney Disease, Hypertension, and Stroke: Insights From a Multivariable Mendelian...

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Genetics

Background:

• Chronic kidney disease (CKD) is a known risk factor for stroke.
• The role of hypertension in mediating the CKD-stroke association requires further clarification.

Purpose of the Study:

• To investigate the causal relationship between CKD, hypertension, and stroke using genetic data.
• To determine the extent to which hypertension mediates the effect of CKD on stroke risk.

Main Methods:

• Utilized genome-wide association study data from European ancestry.
• Employed Mendelian randomization (MR) analyses, including univariable, multivariable, and mediation analyses.
• Examined genetic proxies for CKD (eGFR, UACR), systolic blood pressure (SBP), and cerebrovascular disease.

Main Results:

• Lower estimated glomerular filtration rate (eGFR) was causally associated with increased risk of all stroke, ischemic stroke, and large artery stroke (LAS).
• These associations remained significant after controlling for SBP in multivariable MR analyses.
• Systolic blood pressure mediated only a small proportion (6.5%-7.2%) of the total effect of eGFR on stroke risk.

Conclusions:

• Impaired kidney function (decreased eGFR) has an independent causal effect on stroke risk, especially LAS.
• Preventing kidney disease may offer a strategy to reduce atherosclerotic stroke risk independently of hypertension management.