Kidney damage causally affects the brain cortical structure: A Mendelian randomization study.

Area of Science:

• Neuroscience
• Nephrology
• Genetics

Background:

• Chronic kidney disease (CKD) is associated with brain cortical alterations, but the causal link remains unclear.
• Investigating the causal effect of kidney damage on brain structure is crucial for understanding neurological complications in CKD.

Purpose of the Study:

• To determine the causal effect of kidney damage, including reduced estimated glomerular filtration rate (eGFR), CKD, and albuminuria, on brain cortical structure using Mendelian randomization (MR).
• To explore the relationship between genetic predisposition to kidney damage and alterations in cortical thickness (TH) and surface area (SA).

Main Methods:

• Utilized large-scale genome-wide association studies (GWAS) summary data for eGFR, CKD, and albuminuria from the CKDGen Consortium and UK Biobank.
• Employed MR analysis with inverse-variance weighted (IVW) as the primary method, alongside MR-Egger and weighted median, to assess causality.
• Analyzed brain cortical TH and SA data from the ENIGMA Consortium using magnetic resonance imaging (MRI) in 51,665 individuals.

Main Results:

• Albuminuria was found to causally decrease global cortical thickness (TH) (β = -0.07 mm, P = 0.004).
• Specifically, albuminuria reduced TH in the pars opercularis gyrus (β = -0.11 mm, P = 3.74×10⁻⁶).
• No significant pleiotropy was detected, supporting the robustness of the findings.

Conclusions:

• Kidney damage, particularly albuminuria, exerts a causal influence on brain cortical structure.
• The findings support the existence of a significant kidney-brain axis, highlighting the impact of renal health on neurological integrity.