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Kidney Week

Abstract: TH-PO1065

Lower Estimated Glomerular Filtration Rate Is Associated with Cognitive Decline and Longitudinal Structural Brain Changes over Six Years

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Rahayel, Shady, Universite de Montreal, Montreal, Quebec, Canada
  • Goupil, Remi, Universite de Montreal, Montreal, Quebec, Canada
  • Genest, Suzanne Dominique, Universite de Montreal, Montreal, Quebec, Canada
  • Lamarche, Florence, Universite de Montreal, Montreal, Quebec, Canada
  • Agharazii, Mohsen, Universite de Montreal, Montreal, Quebec, Canada
  • Madore, Francois, Universite de Montreal, Montreal, Quebec, Canada
Background

Chronic kidney disease (CKD) is characterized by albuminuria and/or reduced estimated glomerular filtration rate (eGFR). CKD is linked to cognitive deficits and structural alterations, such as brain atrophy. The mechanisms connecting decreased kidney function, cognitive impairment, and brain function are not yet fully understood. Here, we examined the correlation between eGFR, cognition, and longitudinal brain structure.

Methods

We analyzed a population-based sample of 15,897 participants (53.9 ± 7.5 years old, 49% women) from the CARTaGene cohort in Quebec, Canada. We conducted multivariate linear regressions to explore the relationship between baseline eGFR and cognitive performance. Vertex-based cortical surface analysis was done on the T1-weighted brain MRI scans acquired in 1367 participants six years after baseline to examine whether cortical thickness associated with baseline eGFR adjusting for age, sex, body mass index, vascular risk factors, and white matter lesion volume. Gene set enrichment analysis was done to identify the genetic features of regions where eGFR associated with thickness.

Results

Cognitive performance declined with decreasing eGFR after adjusting for age, sex, income, education, smoking, alcohol intake, vascular risk factors, body mass index, and psychoactive medication use (P<0.001). Lower eGFR associated with cortical thinning in frontal and posterior regions and with increases in the temporal and cingulate areas (Figure 1). Brain regions exhibiting lower eGFR-associated thinning were enriched for mitochondrial gene expression, whereas regions with increased thickness were enriched for genes involved in protein-containing complex remodeling, with apolipoprotein E and angiotensinogen being key elements.

Conclusion

Baseline eGFR is associated with cognition and longitudinal brain structural changes in regions with specific gene expression characteristics.

Brain maps showing the regions where lower eGFR was significantly associated with cortical thinning.

Funding

  • Government Support – Non-U.S.