The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study

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 a...

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Main Authors: Jianbo Qing, Yiting Zhao, Junnan Wu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486564
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author Jianbo Qing
Yiting Zhao
Junnan Wu
author_facet Jianbo Qing
Yiting Zhao
Junnan Wu
author_sort Jianbo Qing
collection DOAJ
description 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.
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spelling doaj-art-c014149051444a1385b18c6a7fa8e2df2025-08-20T02:12:23ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2486564The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization studyJianbo Qing0Yiting Zhao1Junnan Wu2Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaBackground 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.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486564Chronic kidney diseaseimmune cell phenotypesT cellmendelian randomizationimmunotherapy
spellingShingle Jianbo Qing
Yiting Zhao
Junnan Wu
The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
Renal Failure
Chronic kidney disease
immune cell phenotypes
T cell
mendelian randomization
immunotherapy
title The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
title_full The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
title_fullStr The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
title_full_unstemmed The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
title_short The impact of rising peripheral blood naïve CD8+ T cell levels on chronic kidney disease onset: a Mendelian randomization study
title_sort impact of rising peripheral blood naive cd8 t cell levels on chronic kidney disease onset a mendelian randomization study
topic Chronic kidney disease
immune cell phenotypes
T cell
mendelian randomization
immunotherapy
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486564
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