Clearance Of Plasma Mitochondrial DNA By Continuous Venovenous Hemofiltration In Critically Ill Patients

Objective:In recent years,many studies have reported that mitochondrial DNA(mtDNA)plays an important role as damage associated molecular paterns(DAMPs)in a variety of diseases,and has diagnostic and predictive value in severe patients.However,these studies did not consider those critically ill patients who need continuous venovenous hemofiltration(CVVH)intervention in clinic.If we can understand the clearance efficiency of CVVH technology for plasma mtDNA,we can provide a new theoretical basis for evaluating the accuracy of mtDNA diagnosis and predictive value of patients receiving CVVH treatment.Here,we confirmed the effect of CVVH technology on mtDNA through experiments,and calculated the clearance efficiency,so as to provide a new theoretical reference for the clinical evaluation of the role of mtDNA in diseases under CVVH environment and the application of mtDNA as a biomarker.Methods:Twenty-two severe patients who received CVVH treatment from September 2018 to December 2019 in the intensive care unit(ICU)of our institution were consecutively enrolled in the study as study group.Ten healthy volunteers were set up as control group.Obtaining prefilter,postfilter,and ultrafiltrate samples at the initiation of CVVH and repeated after 6 h,12 h(T0,T6,T12,respectively).The mtDNA content was measured by polymerase chain reaction(PCR),and the Mass removal rate(Mtr),Mass adsorption rate(Mad),Sieving coefficient(SC),Plasma clearance(PC)was calculated based on the mass conservation principle.Results:1.Median plasma mtDNA concentration of patients at inlet was significantly higher than healthy volunteers at T0.Plasma mtDNA concentration of patients at inlet was significantly higher than healthy volunteers at T0[13.77(12.45-15.86)ng/mL versus 1.24(1.15-1.34)ng/mL Z=-4.47,p<0.001].2.During CVVH,the level of mtDNA at the inlet decreased significantly with the development of CVVH.The concentration of mtDNA at the inlet decreased.T0:13.77(12.4515.86)ng/mL,T6:14(10.46-15.8)ng/mL,T12:10.54(6.85-15.27)ng/mL,(F=4.3,p=0.02)According to the law of mass conservation,the clearance rate of plasma mtDNA by CVVH in 12h was 25.9%.3.There was no change of the level of mtDNA at the outlet and ultrafiltrate during CVVH.There was no significant change in mtDNA concentration at outlet and ultrafiltrate with CVVH(outlet:F=2.12,p=0.13;ultrafiltrate:F=0.17,p=0.84)4.During CVVH the mtDNA levels at outlet was significantly lower than that at inlet at the same time piont.At the same time point,the median plasma mtDNA concentration at the outlet was significantly lower than that at the inlet[T0:13.77(12.45-15.86)ng/mLversus11.55(9.84-14.26)ng/mL,Z=-2.58,p=0.01;T6:14(10.46-15.8)ng/mLversus 11.32(7.55-12.75)ng/mL,Z=-2.97,p=0.003;T12:10.54(6.85-15.27)ng/mLversus8.5(5.76-10.54)ng/mL,Z=-2.46,p=0.02].5.Finally,no change was seen in the total mass removal rate,total mass adsorption rate,plasma clearance and sieving coefficient over time.According to the law of mass conservation,the changes of Mtr,Mad,SC and PC in the whole process were not statistically significant.(Mtr:x2=1.68;Mad:x2=2.25;SC:x2=3.96;PC:x2=2.04,p>0.05).Conclusions:1.The 12 h clearance rate of mtDNA by CVVH was 25.9%.2.CVVH can clear mtDNA and has therapeutic effect.3.CVVH can affect the value of mtDNA as a biomarker in the diagnosis and prediction of critically ill patients.