Association between Serum Iron Store Biomarkers and All-Cause Mortality in Japanese Patients Undergoing Hemodialysis: A Nationwide Cohort Study.

Introduction: We evaluated the association between iron-related biomarkers - key indicators of iron metabolism and inflammation, and crucial in the management of anemia in patients undergoing hemodialysis - and all-cause mortality. This study aimed to clarify the nuanced relationship between these biomarkers and mortality outcomes, addressing the limitations of traditional cutoff-based analyses.

Methods: We conducted a cohort analysis of patients undergoing dialysis across Japan using data from the Japan Renal Database collected between 2019 and 2020. Patients who had been on dialysis for at least 3 months by the end of 2019 were considered eligible. The associations between iron-related biomarkers and all-cause within 1 year were analyzed using Cox proportional hazards models. The relationship between each biomarker and outcome was illustrated using restricted cubic spline curves, while the combined association of serum ferritin and transferrin saturation (TSAT) with mortality was shown using contour plots.

Results: A total of 215,927 patients were included in the analysis. During the follow-up period, 17,803 (8.24%) deaths were recorded. Contour plots demonstrated increased mortality risk in areas with low ferritin and TSAT levels. Additionally, even in regions with high TSAT levels, there was a trend toward increased mortality risk with increasing ferritin levels. Conversely, in areas with low ferritin levels, there was a trend toward a decreased risk of death with increasing TSAT.

Conclusions: Our findings highlight the complex interplay between serum ferritin and TSAT levels, emphasizing the limitations of relying on single cutoff values for clinical decision-making. The study underscores the need for individualized approaches to iron management in patients undergoing hemodialysis.