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Exploring the Relationship Between Immune Cells and Chronic Kidney Disease by Mendelian Randomization, Colocalization
Huiling Zhu1, Chaofan Qin2, Si Cheng2
1Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Mediators of Inflammation
|April 24, 2025
Summary
Mendelian randomization revealed specific immune cells influencing chronic kidney disease (CKD) risk. Certain T cells increase CKD risk, while myeloid dendritic cells and naive CD4+ T cells offer protection, guiding future prevention strategies.
Area of Science:
- Immunology
- Genetics
- Nephrology
Background:
- Chronic kidney disease (CKD) affects millions globally, with immune factors implicated but their causal link unclear.
- Understanding the role of immune cells in CKD pathogenesis is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the potential causal relationship between 731 immune cell types and the risk of developing CKD.
- To identify specific immune cell markers and their associated genes that may serve as therapeutic targets for CKD.
Main Methods:
- A comprehensive Mendelian randomization (MR) analysis was employed to assess causal associations between immune cells and CKD.
- Sensitivity analyses, including Cochran Q test, leave-one-out, MR-Egger, and MR-PRESSO, were performed to ensure result validity.
- Bidirectional, multivariable, colocalization, and Summary data-based MR (SMR) analyses were utilized to explore causality, confounding, and key gene identification.
Main Results:
- Univariable MR identified 14 risk and 6 protective immune cell factors for CKD.
- After multivariable adjustment, CD28 on CD28+ CD45RA+ CD8+ T cells were identified as a risk factor (OR: 1.112), while CD11c on myeloid dendritic cells (OR: 0.854) and CD45RA on naive CD4+ T cells (OR: 0.918) were protective.
- Colocalization and SMR analyses pinpointed key genes like BACH2, HLA-G, and PAQR9 associated with these immune cells and CKD risk.
Conclusions:
- Mendelian randomization analysis establishes a significant causal link between specific immune cells and chronic kidney disease.
- Key genes such as BACH2, HLA-G, and PAQR9 are identified as potentially crucial in the immune cell-CKD relationship.
- These findings provide valuable insights for the prevention and management of CKD, warranting further mechanistic studies.
