Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis.
Ren Fail
; 46(2): 2367028, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-39010723
ABSTRACT
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 relationship.RESULT:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Inquéritos Nutricionais
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Insuficiência Renal Crônica
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Análise da Randomização Mendeliana
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Fragilidade
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article