Effects of DAMPs level changes following CVVH therapy on outcomes in AKI patients with sepsis

Author(s):

Jie Wu; Jianan Ren; Qinjie Liu; Qiongyuan Hu; Xiuwen Wu

Background:

Damage-associated molecular patterns (DAMPs) were released by injured cells can alarm of tissue damage and activate cellular receptors leading to downstream inflammation, which plays a role in sepsis. Continuous veno-venous hemofiltration (CVVH) has been suggested to play a part in immunomodulation by cytokine removal.

Hypothesis:

To investigate whether the magnitude of DAMPs’ removal is associated with mortality in patients with sepsis on CVVH.

Methods:

We analyzed 26 AKI patients with sepsis and 10 without sepsis. The levels of circulating DAMPs (mitochondrial DNA, mtDNA; nuclear DNA, nDNA; heat shock protein 70, HSP70) and cytokines (IL-1b, IL-6, IL-10, TNF-a, IFN-r) were measured at the beginning, 6h and 12h of CVVH at both inlet and outlet. MtDNA levels were quantified by using mtDNA genes D-loop and ND2. GAPDH and b-globin were used for nDNA levels quantifacation. Urinary DNA levels were analyzed at the beginning and the end of CVVH. Clearance rates during the initial 12 hours of CVVH were calculated. Clinical and laboratory data were acquired from patient’s records data.

Results:

Compared with AKI patients without sepsis, patients with sepsis showed older age(48.9±13.9 vs. 37.3±9.4, p=0.046) and a higher tendency in terms of APCHEII score and SOFA score (p=0.089; p=0.132). 18 sepsis patients (69.2%) and one patients (14.3%) without sepsis died (p=0.026). Baseline of cytokines and DAMPs levels were comparable. Reduction in circulating level of TNF-a (p=0.039) was found in both two groups, while there are no differences in other measured cytokines during the CVVH. MtDNA levels were increased (ND2 p=0.026; D-loop p=0.008) while the HSP70 level was decreased in sepsis patients (p=0.01). Comparing outlet with inlet, we also observed the mtDNA levels were rising after blood passing the filter. The ROC curve indicated that HSP70 clearance rate performed a considerable prediction efficiency for mortality (AUC=0.924, p=0.000). The Multivariable analysis showed that high level of HSP70 clearance rate was a significant independent predictor of mortality (OR=1.127, CI: 1.010-1.257, p=0.032). Urinary nDNA levels (b-globin) before CVVH was identified as an independent prognostic biomarker for duration of CVVH in sepsis patients in multivariate analysis (OR= -1.623, CI: -2.319- -0.928, p=0.000).

Conclusions:

CVVH is valuable for sepsis patients with AKI in part via cytokine removal. However, mtDNA levels are increased after blood passing the filter and survival decreases significantly with higher HSP70 clearance rate. It provides novel mechanisms that allow physicians to improve the outcomes by interfering with it.