Liu Mingjie, Zhou Xuan, Xu Han, Wang Yan, Duan Yuting, Guo Xiangru, Wei Bai
Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Front Immunol. 2025 May 30;16:1567367. doi: 10.3389/fimmu.2025.1567367. eCollection 2025.
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.
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, 0.0001). This relationship exhibited a U-shaped pattern with a threshold effect at PIV=800 ( for log-likelihood ratio = 0.003). Renal function indicators significantly mediated this association, with serum uric acid showing the strongest mediating effect (8.32%, 0.0001), followed by estimated glomerular filtration rate (6.91%, 0.0001), blood urea nitrogen (6.64%, 0.0001), and serum creatinine (5.49%, 0.0001). Cancer survivors exhibited significantly lower Klotho levels than non-cancer participants (813.74 ± 8.55 vs. 849.69 ± 5.08 pg/mL; < 0.0001), as well as higher PIV values (320.07 ± 6.58 vs. 299.07 ± 3.44; = 0.0059).
Elevated PIV was found to be significantly associated with lower klotho levels, with renal function indicators playing a mediating role.
klotho已成为衰老过程中一个有前景的生物标志物。虽然已知炎症可调节klotho表达，但泛免疫炎症值（PIV）与血清klotho水平之间的关系尚未得到研究。本研究旨在探讨PIV与血清klotho水平之间的关联，同时探究肾功能参数的潜在中介作用。
使用2007 - 2016年美国国家健康与营养检查调查（NHANES）的数据进行横断面分析。共纳入13406名参与者。采用多元线性回归模型评估PIV与klotho水平之间的关联。使用Boruta特征选择方法确定多变量模型中包含的变量。进行平滑曲线拟合以检验潜在的非线性关系，并使用两段式线性回归模型进行阈值效应分析。进行中介分析以评估肾功能指标的作用。进行分层分析以确定潜在的效应修饰因素。
在对潜在混杂因素进行充分调整后，PIV与血清klotho水平呈显著负相关（β = -0.11，95%CI：-0.15，-0.07，P < 0.0001）。这种关系呈现出U形模式，在PIV = 800时存在阈值效应（对数似然比 = 0.003）。肾功能指标显著介导了这种关联，血清尿酸的中介作用最强（8.32%，P < 0.0001），其次是估计肾小球滤过率（6.91%，P < 0.0001）、血尿素氮（6.64%，P < 0.0001）和血清肌酐（5.49%，P < 0.0001）。癌症幸存者的klotho水平显著低于非癌症参与者（813.74 ± 8.55 vs. 849.69 ± 5.08 pg/mL；P < 0.0001），且PIV值更高（320.07 ± 6.58 vs. 299.07 ± 3.44；P = 0.0059）。
发现PIV升高与klotho水平降低显著相关，肾功能指标起中介作用。
