ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1567367
Association Between Pan-Immune-Inflammation Value and Serum Klotho Levels: A Cross-Sectional Analysis of Renal Function Mediation
Provisionally accepted
- 1Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: Klotho has emerged as a promising biomarker of aging processes.Although inflammation is known to modulate Klotho expression, the relationship between Pan-Immune-Inflammation Value (PIV) and serum Klotho levels has not been investigated. This study aimed to examine the association between PIV and serum Klotho levels while exploring the potential mediating effects of renal function parameters.Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. A total of 13,406 participants were included. Multiple linear regression models were used to evaluate the association between PIV and Klotho levels. Boruta feature selection method was used to identify variables included in the multivariable models. Smooth curve fitting was performed to examine potential non-linear relationships and threshold effect analysis was conducted using a two-piecewise linear regression model. Mediation analysis was conducted to assess the role of renal function indicators. Stratified analyses were performed to identify potential effect modifiers.After fully adjusting for potential confounders, PIV showed a significant inverse association with serum Klotho levels (β=-0.11, 95%CI: -0.15, -0.07, P <0.0001).This relationship exhibited a U-shaped pattern with a threshold effect at PIV=800 (P for log-likelihood ratio = 0.003). Renal function indicators significantly mediated this association, with serum uric acid showing the strongest mediating effect (8.32%, P <0.0001), followed by estimated glomerular filtration rate (6.91%, P <0.0001), blood urea nitrogen (6.64%, P <0.0001), and serum creatinine (5.49%, P <0.0001). Cancer survivors exhibited significantly lower Klotho levels than non-cancer participants (813.74 ± 8.55 vs. 849.69 ± 5.08 pg/mL; P < 0.0001), as well as higher PIV values (320.07 ± 6.58 vs. 299.07 ± 3.44; P = 0.0059).Elevated PIV was found to be significantly associated with lower klotho levels, with renal function indicators playing a mediating role.
Keywords: Pan-Immune-Inflammation Value, Klotho, NHANES, Inflammation, Renal function
Received: 27 Jan 2025; Accepted: 12 May 2025.
Copyright: © 2025 Liu, Zhou, Xu, Wang, Duan, Guo and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bai Wei, Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.