Background: Although presepsin (P-SEP) is an early sepsis biomarker, sepsis is often suspected after starting hemodialysis (HD). To enhance the utility of P-SEP, we investigated whether pre-HD P-SEP levels could be predicted using the P-SEP levels from blood samples collected after starting HD. Methods: We observed P-SEP level changes due to HD and dialyzer passage in HD patients using a dialysis membrane with a β<sub>2</sub>-microglobulin (β<sub>2</sub>-MG) clearance of either ≥50 mL/min (high-flux) or < 30 mL/min (intermediate-flux). We calculated the removal ratios for the elimination of P-SEP or the predicted pre-HD P-SEP levels based on the correction of hemoconcentration. Results: The P-SEP levels significantly decreased at 4 h after starting HD (n = 8) using membranes with a β<sub>2</sub>-MG clearance ≥50 mL/min; the removal ratios at 2 and 4 h were 42.8 ± 7.9% and 58.8 ± 18.4%, respectively. In contrast, the P-SEP levels did not decrease during the passage of dialyzer in 2 patients with a β<sub>2</sub>-MG clearance < 30 mL/min, and the P-SEP levels increased during HD in all patients (n = 10, including the abovementioned 2 patients) with a β<sub>2</sub>-MG clearance < 30 mL/min. The predicted pre-HD P-SEP levels (y) were strongly correlated with the actually measured pre-HD P-SEP levels (x) (R<sup>2</sup> = 0.9562) using the regression equation: y = 1.0987x. Conclusion: The levels of P-SEP with a molecular weight near that of β<sub>2</sub>-MG decreased similarly to those of β<sub>2</sub>-MG during HD using membranes with a β<sub>2</sub>-MG clearance ≥50 mL/min. On the contrary, the levels of P-SEP rather increased during HD with a β<sub>2</sub>-MG clearance < 30 mL/min, suggesting that P-SEP appeared not to be eliminated. Furthermore, the pre-HD P-SEP levels might be predictable by the correction of hemoconcentration using even blood samples collected after starting HD with a β<sub>2</sub>-MG clearance < 30 mL/min.
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