Linking kidney impairment to amygdala volume changes and mental disorders: a Mendelian randomization study

AI Summary

Mendelian randomization demonstrates that kidney dysfunction causally alters amygdala volume.
Lower eGFR linked to altered amygdala (ORs 0.559 to 0.723); CKD associated with increased amygdala traits (ORs 1.042 to 1.059).
Amygdala volume changes increase depression susceptibility; findings robust to pleiotropy and leave one out analyses, and validated in one-sample MR.

AI Summary

BACKGROUND: Mental disorders are highly prevalent among patients with chronic kidney disease (CKD); however, the causal effects of kidney dysfunction on specific brain volume traits and mental disorders remain underexplored.

These associations also linked kidney dysfunction to an increased risk of depression, using two-sample MR across 507 brain volume and 242 mental disorder GWAS datasets.

Basic summary

Kidney Res Clin Pract. 2026 Jun 15. doi: 10.23876/j.krcp.25.282. Online ahead of print.

ABSTRACT

METHODS: In this Mendelian randomization (MR) study, genetic instruments for kidney function and CKD, derived from genome-wide association studies (GWAS) in Chronic Kidney Disease Genetics and the UK Biobank (n = 1,201,909), were utilized for two-sample MR analysis in the discovery phase. Summary-level data from these GWAS provided exposure-outcome associations to calculate causal estimates using the inverse variance weighted method. Validation analysis was conducted using one-sample MR with individual-level data from the UK Biobank.

RESULTS: Two-sample MR identified causal associations (odds ratios [ORs] as point estimates) between estimated glomerular filtration rate (exposures) and amygdala traits (outcomes), with ORs ranging from 0.559 to 0.723 (p < 0.05). Two-sample MR between CKD (exposures) and amygdala volume traits (outcomes) reported ORs ranging from 1.042 to 1.059 (p < 0.05). These associations also linked kidney dysfunction to an increased risk of depression, using two-sample MR across 507 brain volume and 242 mental disorder GWAS datasets. Leave-one-out analyses and pleiotropy tests, including MR Egger, supported the robustness of these findings. Validation analysis confirmed reproducibility using one-sample MR.

CONCLUSION: Our results demonstrate that kidney dysfunction causally alters amygdala volume, increasing susceptibility to mental disorders such as depression. These findings highlight the kidney-brain axis and underscore the importance of integrating mental health screening and interventions into the clinical management of patients with CKD.

PMID:42299453 | DOI:10.23876/j.krcp.25.282

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