Blood purification treatment initiated at the time of sepsis diagnosis effectively attenuates serum HMGB1 upregulation and improves patient prognosis

Abstract

The aim of the present study was to investigate the increase in serum and urine levels of high mobility group box protein 1 (HMGB1) during sepsis and the effect of blood purification treatments on HMGB1 levels and patient prognosis. A total of 40 intensive care patients with sepsis were randomly assigned to different groups (n=10 per group): A control group (sepsis group), a continuous renal replacement treatment (CRRT) group, a hemoperfusion (HP) group and an HP+CRRT group. The blood purification treatments using HP and/or CRRT were performed immediately after the diagnosis of sepsis. HMGB1 levels were measured using ELISA, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores and 30-day survival rates were evaluated. Relative to a healthy control group (n=10), HMGB1 levels were observed to be significantly upregulated during sepsis (P<0.05). Following the initiation of sepsis, serum HMGB1 continued to increase in the sepsis group and was significantly elevated at 24 h (P<0.05), whereas urine HMGB1 levels decreased significantly at 12 and 24 h (P<0.05). Serum HMGB1 levels were significantly positively correlated with APACHE II scores (r=0.7284, P<0.01) and significantly negatively correlated with urine HMGB1 levels (r=-0.5103, P=0.026). Serum HMGB1 levels were significantly reduced in the HP and HP+CRRT groups by 12 and 24 h following the initiation of treatment (both P<0.05). Changes in the urine HMGB1 level differed in each group. Relative to the sepsis group, the APACHE II scores of all blood purification groups were significantly reduced (P<0.05) and the 30-day survival rate of the HP+CRRT group was significantly increased (P=0.0107). The results of the present study indicate that blood purification initiated at the point of diagnosis in patients with sepsis may attenuate serum HMGB1 upregulation, promote urinary excretion of HMGB1 and improve the prognosis of sepsis.

Keywords: blood purification; excretion; high mobility group box protein 1; prognosis; sepsis.

Figure 1.

Serum and urine HMGB1 levels upon diagnosis of sepsis. (A) Serum and (B) urine levels of HMGB1 were measured by ELISA in the different patient groups prior to the initiation of treatment. Data are presented as the mean ± standard deviation. ^#P<0.05 vs. Control. HMGB1, high mobility group box protein 1; CRRT, continuous renal replacement treatment; HP, hemoperfusion.

Figure 2.

Changes in serum and urine HMGB1 levels over 24 h. (A) Serum and (B) urine levels of HMGB1 in the sepsis (no apheresis intervention) group at different time points. Data are presented as the mean ± standard deviation. ^#P<0.05 vs. 0-h value. HMGB1, high mobility group box protein 1.

Figure 3.

Association of serum HMGB1 level with urine HMGB1 level and APACHE II score. Correlations were identified between (A) urine and serum HMGB1 levels, and (B) APACHE II score and serum HMGB1 level in the sepsis (no apheresis intervention) group. HMGB1, high mobility group box protein 1; APACHE II, Acute Physiology and Chronic Health Evaluation II.

Figure 4.

Changes in serum and urine HMGB1 levels in the different patient groups over 24 h. (A) Serum and (B) urine levels of HMGB1 were measured by ELISA at different time points after the initiation of treatments. Data are presented as the mean ± standard deviation. ^#P<0.05 vs. 0-h value; *P<0.05 vs. sepsis group; ^{^}P<0.05 vs. 12-h value. HMGB1, high mobility group box protein 1; CRRT, continuous renal replacement treatment; HP, hemoperfusion.

Figure 5.

APACHE II scores of patients in different groups upon initiation of treatment (0 h) and 24 h thereafter. Data are presented as the mean ± standard deviation. ^&P<0.05 vs. all other groups at 0 h; ^#P<0.05 vs. 0-h value; *P<0.05 vs. sepsis group at 24 h. APACHE II, Acute Physiology and Chronic Health Evaluation II; CRRT, continuous renal replacement treatment; HP, hemoperfusion.

Figure 6.

Survival curves demonstrating the 30-day survival rates of patients in different groups. CRRT, continuous renal replacement treatment; HP, hemoperfusion.