Metabolic Determinants of Systemic Inflammation Dynamics During Hemodialysis: Insights from the Systemic Immune-Inflammation Index in a Single-Center Observational Study

Background/Objective: Systemic inflammation is a hallmark of end-stage renal disease (ESRD) and contributes to the high burden of cardiovascular morbidity and mortality in hemodialysis (HD) patients. The systemic immune–inflammation index (SII), derived from peripheral neutrophil, lymphocyte, and platelet counts, has emerged as a promising biomarker of immune–inflammatory status. This study aimed to assess the acute effect of a single HD session on systemic inflammation and to identify metabolic predictors associated with this response. Methods: In this single-center observational before–after study, 44 chronic HD patients were enrolled. Blood samples were collected immediately before and after a single HD session. SII was calculated as platelet count × neutrophil count/lymphocyte count. Subgroup analyses were conducted based on renal disease etiology and diabetic status. Multivariable linear regression models identified baseline predictors of SII variation. Results: Median SII significantly decreased post-HD in the overall cohort (from 553.4 [342.6–847.5] to 449.1 [342.6–866.6], p = 0.001), with a more pronounced reduction in patients with cardiometabolic etiologies (from 643.4 [353.3–1360.0] to 539.1 [324.8–1083.4], p = 0.007) and diabetes (from 671.1 [408.7–1469.1] to 458.3 [285.7–1184.4], p = 0.028), but not in those with nephroangiosclerosis (p = 0.182). Baseline total cholesterol (p = 0.001) and gamma-glutamyl transferase (p = 0.034) were positively associated with smaller reductions in SII, while higher baseline glycaemia predicted a greater decrease in post-dialysis SII (p = 0.021). Conclusions: HD acutely modulates systemic inflammation, as reflected by reduction in SII. The magnitude of this response is significantly influenced by individual metabolic profiles. These findings highlight the relevance of metabolic–immune crosstalk in ESRD and suggest that SII may serve as a dynamic biomarker integrating inflammatory and metabolic signals, deserving further validation in larger, outcome-driven studies.