Life's Crucial 9 score and chronic kidney disease: insights from NHANES 2005-2018 and the mediating role of systemic inflammation and oxidative stress

Abstract

Background: Chronic kidney disease (CKD) is a growing global health burden, closely linked to metabolic and cardiovascular risk factors. Life's Crucial 9 (LC9) is a novel health assessment tool that expands upon Life's Essential 8 (LE8) by incorporating mental health (depression) as a key component. This study aimed to investigate the association between LC9 and CKD, compare its predictive value with LE8, and explore potential mediating mechanisms.

Methods: This study analyzed data from 16,431 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Logistic regression models were used to assess the association between LC9 and CKD, with comparisons to LE8. Restricted cubic spline models were applied to explore potential nonlinear relationships. Mediation analysis was conducted to evaluate whether systemic inflammation and oxidative stress mediated the association between LC9 and CKD. Receiver operating characteristic (ROC) analysis was performed to compare the predictive performance of LC9 and LE8 for CKD risk.

Results: Higher LC9 scores were significantly associated with a lower risk of CKD in both continuous and quartile-based analyses. A nonlinear relationship was observed between LC9 and CKD risk (P for nonlinearity < 0.001). Mediation analysis indicated that systemic immune-inflammation index (SII) and uric acid partially mediated the association between LC9 and CKD, with mediation proportions of 3.32 and 11.13%, respectively. ROC analysis showed that LC9 and LE8 had comparable predictive abilities for CKD.

Conclusion: Higher LC9 scores are associated with a reduced risk of CKD, with systemic inflammation and uric acid levels partially mediating this relationship. These findings highlight the importance of comprehensive lifestyle and mental health interventions in CKD prevention and management.

Keywords: CKD; LC9; LE8; NHANES; mediation analysis.

Figure 1

Flowchart of procedures for participants selection and inclusion. CKD, chronic kidney disease; LC9, Life’s Crucial 9; LE8, Life’s Essential 8.

Figure 2

The distribution of LC9 (A). The full-adjusted relationship between LC9 and CKD using restricted cubic spline (B). The solid line represents the fitted nonlinearcurve. The area adjacent to the solid line represents the 95% confidence Interval. LC9, Life’s Crucial 9; CKD, Chronic kidney disease; CI, confidence interval.

Figure 3

The modified caption is as follows: Mediation effects of potential mediators in the associations of LC9 with CKD. Panel A shows the general mediation model. Path a represents the association between LC9 and the mediators; path b represents the effect of the mediators on CKD after adjusting for LC9; path c is the direct effect of LC9 on CKD after adjusting for the mediators; path c is the total effect of LC9 on CKD without accounting for the mediators. The Indirect effect is calculated as a x b. Mediation proportion Indirect effect/total effect. Panel B illustrates the mediating effect of SII. Panel C demonstrates the mediating role of Uric acid. Adjust for age, sex, race, body mass index, poverty income ratio, education levels, marital status, smoking status, alcohol consumption, PA total MET, hyperlipidemia, hypertension, diabetes mellitus and cardiovascular disease. CKD, Chronic kidney disease; LC9, Life’s Crucial 9; SII, Systemic Immune-inflammation index; ACME, Average causal mediation effects (Indirect effect); ADE, Average direct effects. *p < 0.005, **p < 0.01, and ***p < 0.001.

Figure 4

The receiver operating characteristic (ROC) curves for the prediction of CKD using LC9 and LE8 are presented. The Z-test of the area under the ROC curve (AUC) is used to assess the significant difference in predictive performance between the prediction models. LC9, Life’s Crucial 9; LE8, Life’s Essential 8.