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. 2024 Nov 26:15:1399832.
doi: 10.3389/fendo.2024.1399832. eCollection 2024.

Association of systemic immune-inflammation index with all-cause and cardio-cerebrovascular mortality in individuals with diabetic kidney disease: evidence from NHANES 1999-2018

Manhuai Zhang #  1   2 , Siyang Ye #  1   2 , Jianbo Li #  1   2 , Meng Zhang  1   2 , Li Tan  1   2 , Yiqin Wang  1   2 , Peichen Xie  1   2 , Huajing Peng  1   2 , Suchun Li  1   2 , Sixiu Chen  1   2 , Qiong Wen  1   2 , Kam Wa Chan  3 , Sydney C W Tang  4 , Bin Li  1   2 , Wei Chen  1   2
Affiliations

Association of systemic immune-inflammation index with all-cause and cardio-cerebrovascular mortality in individuals with diabetic kidney disease: evidence from NHANES 1999-2018

Manhuai Zhang et al. Front Endocrinol (Lausanne). .

Abstract

Background: Emerging evidence suggests a potential role of immune response and inflammation in the pathogenesis of diabetic kidney disease (DKD). The systemic immune-inflammation index (SII) offers a comprehensive measure of inflammation; however, its relationship with the prognosis of DKD patients remains unclear.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, this cross-sectional study involved adults diagnosed with DKD. Cox proportional hazards models were utilized to assess the associations between SII and all-cause or cardio-cerebrovascular disease mortality. Additionally, restricted cubic spline, piecewise linear regression, and subgroup analyses were performed.

Results: Over a median follow-up duration of 6.16 years, 1338 all-cause deaths were recorded. After adjusting for covariates, elevated SII levels were significantly associated with increased risks of all-cause and cardio-cerebrovascular disease mortality. Specifically, per one-unit increment in natural log-transformed SII (lnSII), there was a 29% increased risk of all-cause mortality (P < 0.001) and a 23% increased risk of cardio-cerebrovascular disease mortality (P = 0.01) in the fully adjusted model. Similar results were observed when SII was analyzed as a categorical variable (quartiles). Moreover, nonlinear association was identified between SII and all-cause mortality (P < 0.001) through restricted cubic spline analysis, with threshold value of 5.82 for lnSII. The robustness of these findings was confirmed in subgroup analyses. Likewise, the statistically significant correlation between SII levels and cardio-cerebrovascular disease mortality persisted in individuals with DKD.

Conclusion: Increased SII levels, whether examined as continuous variables or categorized, demonstrate a significant association with elevated risks of all-cause and cardio-cerebrovascular disease mortality among DKD patients. These findings imply that maintaining SII within an optimal range could be crucial in reducing mortality risk.

Keywords: NHANES; all-cause mortality; cardio-cerebrovascular disease mortality; diabetes mellitus; diabetic kidney disease; population-based study; systemic immune-inflammation index.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A flow chart of sample selection of eligible participants from the NHANES 1999-2018.
Figure 2
Figure 2
Restricted cubic spline regression of the relationship between lnSII and all-cause mortality (A) or cardio-cerebrovascular disease mortality (B). SII was assessed in its continuous form after applying a natural log-transformation (lnSII). SII, systemic immune-inflammation index; HR, hazard ratio; 95% CI, 95% confidence interval.
Figure 3
Figure 3
Forest plot for subgroup analysis of associations between lnSII and all-cause mortality. Hazard ratios (HR) were calculated using multivariate Cox proportional hazards models adjusted for variables in model 2 except for the variable used for stratification. SII was assessed in its continuous form after applying a natural log-transformation (lnSII). SII, systemic immune-inflammation index; 95% CI, 95% confidence interval.
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