Zhu Zheng-Yang, Ren Ke-Jun, Duan Xiao-Wei, Hu Xu-Lei, Lv Yong, Wang Dong, Jin Hua, Zhang Lei
The First Clinical Medical College, Anhui University of Chinese Medicine, Hefei City, Anhui Province, China.
The First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei City, Anhui Province, China.
PLoS One. 2025 Aug 1;20(8):e0329315. doi: 10.1371/journal.pone.0329315. eCollection 2025.
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.
本研究利用了2005 - 2020年美国国家健康与营养检查调查（NHANES）的数据（n = 28,231，包括4,907例慢性肾脏病（CKD）患者），进行加权分析，并通过方差膨胀因子（VIF）评估来验证协变量选择，以支持模型有效性，首次证明纤维化-4（FIB4）指数是CKD患者全因死亡和心血管疾病（CVD）相关死亡的独立预测因子。加权逻辑回归证实FIB4指数是CKD风险的显著独立预测因子（完全调整后的优势比（OR）为1.85，95%置信区间（CI）为1.64 - 2.08），具有强剂量反应梯度（Q4的OR为3.51 - 6.02）。多变量Cox比例风险回归模型显示，FIB4指数每增加1个单位，全因死亡风险升高34%（风险比（HR）= 1.34，95%CI：1.27 - 1.41，p < 0.001），CVD死亡风险增加34%（HR = 1.34，95%CI：1.24 - 1.44，p < 0.001）。受限立方样条（RCS）分析在1.84（全因死亡）和1.74（CVD死亡）的拐点处确定了非线性阈值效应，超过这些阈值后死亡风险急剧上升（全因HR = 2.57；CVD HR = 2.85）。受试者工作特征（ROC）曲线分析显示出强大的预测性能（曲线下面积（AUC）：全因死亡为0.799；CVD死亡为0.801）。亚组分析突出了非西班牙裔黑人个体、老年人以及身体活动水平低的人群中风险更高。中介分析表明，中性粒细胞与淋巴细胞比值（NLR）介导了FIB4与全因死亡关联的5.48%以及与CVD死亡关联的5.83%，尽管直接效应占主导（分别为94.52%和94.17%）。这些发现确立了FIB4指数作为CKD患者风险分层的实用、循证工具，为个性化临床管理提供了关键见解。
