Introduction: Chronic kidney disease is associated with cognitive decline and changes in brain structure. However, their associations remain unclear, particularly the selective vulnerability characteristics that make some brain regions more vulnerable. Methods: We investigated the association between eGFR and cognitive function in 15,897 individuals from the CARTaGENE cohort. We performed vertex-based MRI analyses between eGFR and cortical thickness in the 1,397 participants who underwent brain MRI after six years. Imaging transcriptomics was used to characterize the gene expression and neurodegenerative features associated with this association. Results: Lower eGFR correlated with reduced cognitive performance and brain structure. Brain regions associated with eGFR were enriched for mitochondrial and inflammatory-related genes. These associations occurred independently from age, sex, education, body mass index, Framingham risk score, and white matter lesion volume. Discussion: This study highlights the link between reduced eGFR, cognitive impairment, and brain structure, revealing some of the kidney-brain axis mechanisms.

The authors have declared no competing interest.

This study did not receive any funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of the McGill University Health Centre and the Centre integre universitaire de sante et de services sociaux du Nord de l'Ile de Montreal

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Qualified researchers may obtain access to all de-identified imaging data in the biomarkers registry used for this study (https://cartagene.qc.ca).