Abstract
BACKGROUND: The global incidence of chronic kidney disease (CKD) is rising rapidly. Immune cells play a crucial role in the onset and progression of CKD, however, the causal relationships and underlying immunological mechanisms remain incompletely elucidated. This deficiency hinders the development and application of early interventions and immunotherapies for CKD. METHODS: In this study, we hypothesize that alterations in immune cell phenotypes (ICPs) in the blood may influence the onset of CKD. We collated Genome Wide Association Studies (GWAS) data for 731 ICPs, alongside summary data for CKD and estimated glomerular filtration rate (eGFR). Utilizing bidirectional mendelian randomization analysis (MR), we identified the impact of ICPs on the onset of CKD. RESULTS: Preliminary MR analyses revealed three ICPs positively associated with CKD onset: the absolute number of CD45RA(+) CD28(-) CD8(+) T cells (p = 1.209 × 10(-15), 95% CI: 1.0002-1.0003), the percentage of CD28(+) CD45RA(+) CD8(+) T cells of total T cells (p = 5.831 × 10(-6), 95% CI: 1.0028-1.0070), and the percentage of CD45RA(-) CD28(-) CD8(+) T cells of total T cells (p = 4.292 × 10(-5), 95% CI: 1.0005-1.0015). After conducting sensitivity and reverse MR analyses, only the percentage of CD28(+) CD45RA(+) CD8(+) T cells (naïve CD8(+) T Cells) was found to have a sufficiently robust causal impact on CKD. CONCLUSION: We are the first to demonstrate a significant positive association between the percentage of naïve CD8(+) T cells and CKD onset. This finding offers new insights for early prevention and treatment of CKD.