Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis
Background Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous.Methods Our analysis of 7,078 p...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2367028 |
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| author | Guanghao Zheng Yu Cheng Chenlong Wang Bin Wang Xinchang Zou Jie Zhou Lifen Peng Tao Zeng |
| author_facet | Guanghao Zheng Yu Cheng Chenlong Wang Bin Wang Xinchang Zou Jie Zhou Lifen Peng Tao Zeng |
| author_sort | Guanghao Zheng |
| collection | DOAJ |
| description | Background Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous.Methods Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999–2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells’ mediating roles in the FI-CKD relationshipResult Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD.Conclusion Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population. |
| format | Article |
| id | doaj-art-e5275b11f3434a1fb45ca367c19f8cac |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-e5275b11f3434a1fb45ca367c19f8cac2025-08-20T03:05:25ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2367028Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysisGuanghao Zheng0Yu Cheng1Chenlong Wang2Bin Wang3Xinchang Zou4Jie Zhou5Lifen Peng6Tao Zeng7Department of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, 330000, Jiangxi Province, ChinaDepartment of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, 330000, Jiangxi Province, ChinaDepartment of Central Laboratory, The Affiliated Huaian No.1 Peopele’s Hospital, Nanjing Medical University, Huai’an, ChinaDepartment of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, 330000, Jiangxi Province, ChinaDepartment of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, 330000, Jiangxi Province, ChinaDepartment of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, 330000, Jiangxi Province, ChinaMolecular Experiment Center, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital, Nanchang University, Nanchang, ChinaBackground Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous.Methods Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999–2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells’ mediating roles in the FI-CKD relationshipResult Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD.Conclusion Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2367028Chronic kidney diseasefrailty indexrenal functionimmune cellsplasma proteinsmendelian randomization |
| spellingShingle | Guanghao Zheng Yu Cheng Chenlong Wang Bin Wang Xinchang Zou Jie Zhou Lifen Peng Tao Zeng Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis Renal Failure Chronic kidney disease frailty index renal function immune cells plasma proteins mendelian randomization |
| title | Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis |
| title_full | Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis |
| title_fullStr | Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis |
| title_full_unstemmed | Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis |
| title_short | Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis |
| title_sort | elucidating the causal nexus and immune mediation between frailty and chronic kidney disease integrative multi omics analysis |
| topic | Chronic kidney disease frailty index renal function immune cells plasma proteins mendelian randomization |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2367028 |
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