Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.

This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2020 (n = 28,231, including 4,907 chronic kidney disease (CKD) patients) with weighted analyses and, through variance inflation factor (VIF) assessment to verify covariate selection, supported model vali...

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Main Authors: Zheng-Yang Zhu, Ke-Jun Ren, Xiao-Wei Duan, Xu-Lei Hu, Yong Lv, Dong Wang, Hua Jin, Lei Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0329315
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author Zheng-Yang Zhu
Ke-Jun Ren
Xiao-Wei Duan
Xu-Lei Hu
Yong Lv
Dong Wang
Hua Jin
Lei Zhang
author_facet Zheng-Yang Zhu
Ke-Jun Ren
Xiao-Wei Duan
Xu-Lei Hu
Yong Lv
Dong Wang
Hua Jin
Lei Zhang
author_sort Zheng-Yang Zhu
collection DOAJ
description This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2020 (n = 28,231, including 4,907 chronic kidney disease (CKD) patients) with weighted analyses and, through variance inflation factor (VIF) assessment to verify covariate selection, supported model validity, to demonstrate for the first time that the Fibrosis-4 (FIB4) index serves as an independent predictor of all-cause and cardiovascular disease (CVD)-related mortality in CKD patients. Weighted logistic regression confirmed FIB4 index as a significant independent predictor of CKD risk (fully adjusted odds ratios (OR) 1.85, 95% confidence interval (CI) 1.64-2.08), with strong dose-response gradient (Q4 OR 3.51-6.02). Multivariable Cox proportional hazards regression models revealed that each 1-unit increase in the FIB4 index was associated with a 34% elevated risk of all-cause mortality (hazard ratio (HR) = 1.34, 95%CI: 1.27-1.41, p < 0.001) and a 34% increased risk of CVD mortality (HR = 1.34, 95% CI: 1.24-1.44, p < 0.001). Restricted cubic spline (RCS) analysis identified nonlinear threshold effects at inflection points of 1.84 (all-cause mortality) and 1.74 (CVD mortality), with mortality risks escalating sharply beyond these thresholds (all-cause HR = 2.57; CVD HR = 2.85). Receiver operating characteristic (ROC) curve analysis demonstrated robust predictive performance (area under the curve (AUC): 0.799 for all-cause mortality; 0.801 for CVD mortality). Subgroup analyses highlighted heightened risks among non-Hispanic Black individuals, older adults, and those with low physical activity. Mediation analysis indicated that neutrophil-to-lymphocyte ratio (NLR) mediated 5.48% of the FIB4-all-cause mortality association and 5.83% of the CVD mortality association, though direct effects predominated (94.52% and 94.17%, respectively). These findings establish the FIB4 index as a practical, evidence-based tool for risk stratification in CKD patients, offering critical insights for personalized clinical management.
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spelling doaj-art-28efa5a8bf3b46e8add2bfdbc7eb223e2025-08-20T03:39:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01208e032931510.1371/journal.pone.0329315Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.Zheng-Yang ZhuKe-Jun RenXiao-Wei DuanXu-Lei HuYong LvDong WangHua JinLei ZhangThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2020 (n = 28,231, including 4,907 chronic kidney disease (CKD) patients) with weighted analyses and, through variance inflation factor (VIF) assessment to verify covariate selection, supported model validity, to demonstrate for the first time that the Fibrosis-4 (FIB4) index serves as an independent predictor of all-cause and cardiovascular disease (CVD)-related mortality in CKD patients. Weighted logistic regression confirmed FIB4 index as a significant independent predictor of CKD risk (fully adjusted odds ratios (OR) 1.85, 95% confidence interval (CI) 1.64-2.08), with strong dose-response gradient (Q4 OR 3.51-6.02). Multivariable Cox proportional hazards regression models revealed that each 1-unit increase in the FIB4 index was associated with a 34% elevated risk of all-cause mortality (hazard ratio (HR) = 1.34, 95%CI: 1.27-1.41, p < 0.001) and a 34% increased risk of CVD mortality (HR = 1.34, 95% CI: 1.24-1.44, p < 0.001). Restricted cubic spline (RCS) analysis identified nonlinear threshold effects at inflection points of 1.84 (all-cause mortality) and 1.74 (CVD mortality), with mortality risks escalating sharply beyond these thresholds (all-cause HR = 2.57; CVD HR = 2.85). Receiver operating characteristic (ROC) curve analysis demonstrated robust predictive performance (area under the curve (AUC): 0.799 for all-cause mortality; 0.801 for CVD mortality). Subgroup analyses highlighted heightened risks among non-Hispanic Black individuals, older adults, and those with low physical activity. Mediation analysis indicated that neutrophil-to-lymphocyte ratio (NLR) mediated 5.48% of the FIB4-all-cause mortality association and 5.83% of the CVD mortality association, though direct effects predominated (94.52% and 94.17%, respectively). These findings establish the FIB4 index as a practical, evidence-based tool for risk stratification in CKD patients, offering critical insights for personalized clinical management.https://doi.org/10.1371/journal.pone.0329315
spellingShingle Zheng-Yang Zhu
Ke-Jun Ren
Xiao-Wei Duan
Xu-Lei Hu
Yong Lv
Dong Wang
Hua Jin
Lei Zhang
Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
PLoS ONE
title Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
title_full Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
title_fullStr Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
title_full_unstemmed Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
title_short Fibrosis-4 index as a predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease.
title_sort fibrosis 4 index as a predictor of all cause and cardiovascular mortality in patients with chronic kidney disease
url https://doi.org/10.1371/journal.pone.0329315
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