| Objective:Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Epidemiological survey,in recent years,hough the development of anti-infection treatment,early fluid resuscitation and renal replacement therapy,sepsis is still a serious threat to the health of patients with high morbidity and mortality.Among critically ill patients,the incidence rate of severe epsis with acute kidney injury reaches as high as 50%,and compared with those of other reasons caused by AKI,caused by sepsis AKI performance instability of emodynamics and more pressor agents and higher proportion of patients requiring mechanical ventilation,higher disease severity score,mortality is also higher.Sepsis and inflammatory had a thousand and one links.Inflammation is the body's defensive response to traumatic injury,the characteristics of the inflammatory response trigger of the inflammatory cell activation involved in the inflammatory response,including neutrophils,monocyte and endothelial cells,etc.Neutrophils and monocytes cells ave the power of phagocytosis and antigen presented in early stage of inflammation,constituting a defense of the inflammatory response.Moderate inflammatory response is beneficial to human body,but when the body's own adjustment disordered in the process of inflammatory,could cause inflammation out of control,to make it happen the amplification effect of cascade,lead to more serious damage to itself.Granulocyte/monocyte aphersis is an adsorption column whose adsorption carrier is cellulose cetate beads.and peripheral blood meets beads in adsorbed phase,GMA has elective sorption to neutrophils and monocytes,and without the of adsorption red blood cells,platelets and lymphocytes.In order to explore the method of treating sepsis/septic acute kidney injury by adsorbing the source of inflammation,this esearch chooses granulocyte/monocyte apheresis(GMA)treatment,through the cecal ligation and puncture(CLP)in the rats model of sepsis,explore GMA function and he mechanism of treatment of sepsis AKI in rats.To evaluated the prognostic value of prealbumin levels in patients with acute kidney injury(AKI),which reason for causing AKI is acute tubular necrosis.Materials and methods:after 20 hours of cecal ligation and puncture in rats stablishing extracorporeal circulation and the blood flow control in 0.8-1.0 ml/min.The granulocyte/monocyte apheresis(GMA)group,extracorporeal circulation of hole blood and cellulose acetate beads as adsorption carrier,then returned it to the body.The treatment lasts for 2 hours.At the same time,the Sham GMA group,namely the CLP in extracorporeal circulation same 20 hours after contact with cellulose acetate beads adsorption column,followed by whole blood again back to the body.Setting up control group,only do laparotomy,closed abdomen after separation and exposed of cecum,no cecal ligation and puncture,20 hours later,to separate and exposure blood vessels,no extracorporeal circulation.48 hours after CLP,part of rats put to death.Blood samples and tissue specimen were collected before and after the circulation,keeping blood and related organization.Part of rats continuous observation,Survival time was assessed up to 7 days.This was a prospective cohort study.Hospital-acquired AKI patients in the Ninth People's Hospital from February2012 to June 2014.laboratory measurements and clinical data were recorded.Cox proportional hazards model was uesd to estimate the risk of the ninety days mortality associated with serum prealbumin level at the beginning of the nephrology consultation.Results:Granulocyte/Monocyte apheresis(GMA)altered the natural history of sepsis in rats.GMA intervention group after 2 hours circulation when peripheral white blood cell count less than the number before intervention((4.14±1.30)×10~9/L vs(9.65±2.13)×10~9/L,p<0.05),and less than that of sham treatment group((4.14±1.30)×10~9/L vs(8.36±3.02)×10~9/L,p<0.05).Among them,the of neutrophils and monocytes decreased obviously(p<0.05).Through detecting CD11b~+expression intensity in the peripheral blood leukocytes,after 2 hours intervention,GMA group CD11b~+average fluorescence intensity decreased obviously,which reminder reduced the number of granulocytes and monocytes,difference was statistically significant(p<0.05).After CLP,the seven days survival rate of sham GMA rats was only 46.7%,in the GMA group which was increased to 73.3%(p<0.05).Alanine aminotransferase,aspartate aminotransferase and urea nitrogen levels decreased significantly after the treatment of GMA(p<0.05).The renal and liver pathological injury score showed significant reduced in tissue damage(p<0.05).Also GMA obviously alleviate the acute injury score of lung(p<0.05).Reduced the lung tissue inflammatory cell infiltration and inflammatory reaction of lung tissue.Neutrophils infiltration into the lung tissue after GMA treatment,compared with the sham GMA group of 31.28±11.12%,dropped to 22.11±10.02%(p<0.05).Macrophage infiltration in tissue decreased obviously(p<0.05).the total cells number in BALF decreased significantly compared with the sham GMA group(p<0.05),GMA treatment could improve the pulmonary vascular permeability,The concentration of total proteins in bronchoalveolar lavage fluid(BALF)of GMA group could be reduced to 335.14±102.09?g/mL,while in the Sham GMA group which was still as high as 563.92±374.61?g/mL(p<0.05).and TNF-?,IL-6,IL-10 levels and the level of TNF-?in BALF were significantly decreased(p<0.05).And serum IL-1?,IL-6,IL-10 present significant decreased.GMA treatment had no effect on the adaptive immunity,which does not change the rate of CD4~+T lymphocytes and CD8~+T lymphocytes both in spleen and blood.Three hundreds and forty-eight hospital-acquired AKI patients matched at least one of the Risk,Injury,Failure,Loss,End Stage(RIFLE)criteria for increased serum creatinine,and had requested a nephrology consultation.Clinicopathologic variables were compared between patients with a serum prealbumin level,<13.6 mg/dL(the exposed group;cutoff point,median)and patients with a serum prealbumin level?13.6 mg/dL(the control group).In-hospital mortality rates associated with prealbumin levels were 48.3%for<13.6 mg/dL,and 21.4% for?13.6mg/dL(?~2=13.622,P<0.001).After adjusted analysis age,sex,hemoglobin,serum albumin,C-reactive protein,Liano score and serum total cholesterol,the presence of a serum prealbumin level,<13.6mg/dL was significantly associated with increased the ninety days mortality(hazard ratio(HR)=1.784;95%confidence interval:1.059 to 3.006,P=0.029).In addition,each increment of 5 mg/dL of serum prealbumin was associated with an adjusted 24%decrease of the ninety days mortality(hazard ratio(HR)=0.754;95%confidence interval:0.606-0.938 P=0.011).Conclusions:Granulocyte/Monocyte apheresis for sepsis AKI rats has a certain therapeutic effect,through adsorbs neutrophils and monocytes,in particular,the activation of neutrophils,reduces the secretion of pro-inflammatory factors,alleviates neutrophils and macrophages infiltration,and then prolong the survival time of rats,ameliorate organ function.Low level of serum prealbumin was an independent risk factor of death in hospital-acquired AKI patients. |
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