Effects of Changes in the Levels of Damage-Associated Molecular Patterns Following Continuous Veno-Venous Hemofiltration Therapy on Outcomes in Acute Kidney Injury Patients With Sepsis.

Abstract

Background: We investigated the association of damage-associated molecular pattern (DAMP) removal with mortality in sepsis patients undergoing continuous veno–venous hemofiltration (CVVH).Methods: Circulating levels of DAMPs [mitochondrial DNA (mtDNA); nuclear DNA (nDNA); heat shock protein 70 (HSP70); and high mobility group box 1 (HMGB1)] and cytokines were measured at baseline, 6 and 12 h after initiation of CVVH. Urinary DNA levels were analyzed at baseline and end of CVVH. The expression of human leukocyte antigen (HLA)-DR was assayed at 0, 3, and 7 days after initiation of CVVH. Moreover, the effects of HSP70 and HMGB1 clearance on survival were analyzed.Results: We evaluated 43 patients with acute kidney injury (AKI) (33 sepsis patients). Twenty-two sepsis patients (67%) and three non-sepsis patients (30%) expired (P = 0.046). Significant reductions in the levels of circulating interleukin-6 (P = 0.046) and tumor necrosis factor-α (P = 0.008) were found in the sepsis group. The levels of mtDNA were increased (ND2, P = 0.035; D-loop, P = 0.003), whereas that of HSP70 was reduced (P = 0.000) in all patients during the first 12 h. The levels of DAMPs in the plasma were markedly increased after blood passage from the inlet through the dialyzer in survivor sepsis patients. The clearance rates of HSP70 and HMGB1 were good predictors of mortality [area under the curve (AUC) = 0.937, P = 0.000; AUC = 0.90, P = 0.001, respectively]. The level of HLA-DR was increased in response to higher HSP70 clearance (P = 0.006). Survival was significantly worse in groups with higher clearance rates of HSP70 and HMGB1 than the cut-off value (log-rank test: P = 0.000 for both). Higher HSP70 clearance was a significant independent predictor of mortality (odds ratio = 1.025, 95% confidence interval [CI]: 1.012–1.039, P = 0.000). The urinary nDNA (β-globin) level before CVVH was an independent risk factor for the duration of CVVH in patients with sepsis (sRE = 0.460, 95% CI: 1.720–8.857, P = 0.005).Conclusion: CVVH removes inflammatory factors, reduces urinary DAMPs, and removes plasma DAMPs. However, survival decreases in response to higher HSP70 clearance.