Effects Of Hemodialysis And Hemoperfusion Combined Treatment On The Micro-inflammation Stress In Maintenance Hemodialysis Patients

Many studies have reported that dialysis-related pathology (DRP) is one of the most common causes to increase the end-stage renal disease mortality and morbidity in long-term hemodialysis patients. Cardiovascular disease (CVD) is the main clinical manifestations of DRP,which is the principal cause of death in patients with end-stage renal disease, and most CVD are derived from atherosclerosis (AS) complications. AS is an inflammatory process, even in early renal failure, there AS lesions, and non-dialysis renal failure patients with elevated C-reactive protein (CRP) may be prompted to the presence of AS. As we all know, middle molecule or macromolecular toxins and chronic micro-inflammatory closely related to the each other in uremia.So chronic micro-inflammatory state is a major factor in DRP.As oxidative metabolism and oxygen radical scavenging systems were damaged, the oxidation and antioxidant, inflammation and anti-inflammatory imbalance informed in hemodialysis patients, with the levels of advanced oxidation protein products (AOPP), advanced glycation end products (AGE),β2-microglobulin (β2-MG), homocysteine (Hcy), cystatin C (CysC), intact parathyroid hormone (iPTH) increased while CRP increased too;At the same time, The use of dialyzers and dialysis fluid bacterial derivatives can stimulate the synthesis and release of monocyte pro-inflammatory factors, such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin 18 (IL-18), tumor necrosis factor (TNF-α) and other levels increase, CRP, has also increased. however, conventional hemodialysis can not be removed or micro-cleared, and even increase these middle molecule or macromolecules uremic toxins,which are the key media of long-term hemodialysis treatment of acute or chronic inflammatory diseases.Owing to financial and technical requirements, A number of attempts in domestic and foreign to remove uremic toxin molecules were proved to be not suitable for hemodialysis treatment in patients with an ideal. Hemoperfusion (HP) technology, which in vitro leads to the patient's blood into the perfusion device, through the adsorbent adsorption removal of exogenous and endogenous toxins, to achieve the purpose of hemodialysis, is relatively inexpensive, easy to use.Studies have shown that resin-based hemoperfusion combined with hemodialysis were able to compensate for the deficiencies of conventional hemodialysis, Thereby reducing uremic toxins and thus reduce the maintenance hemodialysis patients with micro-inflammation, improve nutrition, enhance the long-term hemodialysis patients quality of life.Objective:This study aimed to investigate whether hemoperfusion combined with hemodialysis could affect the level of a number of middle or macromolecules uremic toxins in the maintenance hemodialysis patients. At the same time, whether it helps to reduce uremic toxins in turn reduce the maintenance hemodialysis patients with micro-inflammation and reduce cardiovascular complications. Determination of indicators,such as CRP, IL-8, IL-18, AOPP, AGE, Hcy, CysC, iPTH,β2-MG,to further explore the blood perfusion to the maintenance of hemodialysis patients the relationship between the micro-inflammatory state, as well as their associated factors.Methods:1.Fisrt select case:94 cases of patients treated with maintenance hemodialysis in our hospital's hemodialysis center in a stable condition, dialysis age≥3 months, to exclude acute infection, vasculitis, hepatitis virus carriers and other active disease,and all the patient informed consent. Conventional hemodialysis treatment three times a week, every 4 hours, the application unfractionated heparin or low molecular weight heparin anticoagulation.2.Second select case and experimental design:Select 10(10/94) cases of illness and the relative stability of C-reactive protein greater than 8mg/L(Biochemical room recognizes this value as a cut-off point) of maintenance hemodialysis patients(Hemoperfusion+hemodialysis, the experimental group). Choose Another 10 cases of C-reactive protein less than 8mg/L match with the experimental group than in the maintenance hemodialysis patients(Simple hemodialysis, the control group).Experimental group,6 males and 4 females, with an average age of 60.300±10.594 years,and Primary disease chronic glomerulonephritis in 6 cases, benign arteriolar nephrosclerosis in 2 cases,2 cases of diabetes, dialysis age of 41.400±34.552 months.; and 6 males and 4 females, with an average age of 61.500±15.551 years old, the incidence of chronic glomerulonephritis,5 cases of benign arteriolar nephrosclerosis in 3 cases,2 cases of diabetes, dialysis age of 45.200±34.298 months in control group. Its parameters were not significantly different (P≥0.343). Gambro dialysis machines, dialyzers were polyamide membrane 1.4m2, a one-time use, dialysis fluid flow rate 500ml/min, blood flow rate200-250ml/min,Bicarbonate dialysate, arteriovenous fistula use. Two groups of conventional hemodialysis treatment for 3 months,3 times a week, every 4 hours, the application unfractionated heparin or low molecular weight heparin anticoagulation. Then the experimental group of conventional hemodialysis treatment+hemoperfusion treatment for 3 months,1 week, hemoperfusion 130g (Jafron Biomedical Co., Ltd.), and the other two sub-conventional hemodialysis treatment, anticoagulant use ibid. Select the patient observation time 0 month,3 months,6 months, patients taking the blood, and as soon as possible indicators of the test line, no test specimens in the centrifugal cryogenic refrigerator (-70℃) to save.3.Uremic toxins, inflammation indicators Detection:AOPP was measured by fluorescence spectrophotometry, AGE was measured by fluorescence spectrophotometry, IL-8, IL-18, iPTH, P2-MG were measured using ELISA,and CRP, ALB, cystatin C (CysC) measured by our routine hospital clinical laboratory:CRP using immune turbidimetry, ALB using bromocresol green method, latex enhanced nephelometric immunoassay to detect CysC.4. Statistical analysis:Results are expressed as mean±standard deviation (x±S). The repeated measureANOVA was used for each repeated measure parameter. Multiple comparisons between groups using LSD test; If the Mauchly test of sphericity results of≤0.05, then the right degree of freedom for Greenhouse-Geisserεcorrection. Any of these two parameters, the correlation between choice correlation coefficients indicated. Statistical significance was defined at P<0.05.All data is SSPS16.0 statistical software for analysis and processing.Results1.Maintenance hemodialysis patients with CRP levels of change:HD group CRP levels 0m,3m,6m, respectively (2.070±1.018,2.900±2.096,2.980±2.355) mg/L,as the prolonged dialysis gradually increased, but three times were no significanly different (P>0.05).HD+HP group CRP levels 0m,3m, 6m, respectively (18.610±12.712,23.600±12.160,10.910±7.143) mg/L, three times were significantly different (P<0.01).2. Maintenance hemodialysis patients with others uremic toxins levels of change:HD group IL-8 levels 0m,3m,6m, respectively (207.475±101.871,244.089±78.975,270.107±95.345)pg/ml,as the prolonged dialysis gradually increased, but three times were significantly different (P<0.01).HD+HP group IL-8 levels 0m,3m,6m, respectively (631.665±94.156,705.142±112.811,467.819±133.332) pg/ml, three times were significantly different (P<0.01).HD group IL-18 levels 0m,3m,6m, respectively (735.839±31.333,766.010±36.983,791.535±33.922)pg/ml,as the prolonged dialysis gradually increased, but three times were significantly different (P<0.01).HD+HP group IL-18 levels 0m,3m,6m, respectively (804.770±35.322,861.440±53.998,704.583±74.092)pg/ml, three times were significantly different (P<0.01).HD groupβ2-MG levels 0m,3m,6m, respectively (195.210±78.358. 185.850±67. 011,208.587±76.259)ng/l, three times were no significantly different(P>0.05).HD+HP groupβ2-MG levels 0m,3m,6m, respectively (280.000±78.183.305.430±71.746.283.620±52.994)ng/l,three times were no significantly different(P>0.05).HD group AOPP levels Om,3m,6m,respectively(81.300±20.391.94.200±23.203.90.000±19.810)μmol/l,three times were no significantly different (P>0.05).HD+HP group AOPP levels Om,3m,6m,respectively(107.800±40.124,114.500±25.444.112.900±39.968)μmol/l,three times were no significantly different(P>0.05).HD group AGE levels 0m,3m,6m,respectively(193.710±32.861. 194.790±32.581.189.230±38.719)int,three times were no significantly difference (P>0.05).HD+HP group AGE levels Om,3m,6m, respectively(195.460±44.917.205.140±32.327.189.650±35.439)int,three times wereno significantly different(P>0.05).HD group AGE levels Om,3m,6m,respectively(193.710±32.861 194.790±32.581.189.230±38.719)int,three timeswere no significantly difference (P>0.05).HD+HP group AGE levels Om,3m,6m, respectively(195.460±44.917.205.140±32.327.189.650±35.439)int,there times were no significantly different(P>0.05).HD group CysC levels 0m,3m,6m,respectively(8.287±0.856.8.757±0.782.8.553±0.931)g/l there was no significantly different(P>0.05).HD+HP group CysC levels 0m,3m,6m,respectively(8.516±1.237.9.320±0.798.8.261±1.089)g/l,there times were significantly different(P>0.05).HD group i PTH levels 0m,3m,6m,respectively(507.700±275.407.702.640±419.405.722.120±459.635)pg/ml,there times were significanlyt different (P>0.05).HD+HP group i PTH levels 0m,3m,6m,respectively(780.530±736.789.966.160±767.424.859.780±811.049)pg/ml,there times were significantly different(P<0.01). 3 in maintenance hemodialysis patients with dialysis adequacy (Kt/V) changes:HD group of Kt/V level of Om,3m,6m, respectively (1.228±0.127,1.233±0.113,1.233±0.131), with the prolonged dialysis were no significant difference (P> 0.05).HD+HPgroup Kt/V levels of 0m,3m,6m, respectively (1.257±0.167, 1.289±0.107,1.5312±0.113), three times were significantly different (P< 0.01).4 maintenance hemodialysis patients with serum albumin (Alb) changes:HD group Alb level 0m,3m,6m, respectively (35.980±0.611,36.040±0.622, 36.110±0.633)g/L, with the prolonged dialysis was no significantly different (P>0.05). HD+HP group Alb levels 0m,3m,6m, respectively (35.410±0.876, 35.490±0.955,36.890±0.939)g/l, three times were significantly different (P< 0.01).5 using the correlation analysis to exclude the impact of the remaining variables:0m, CRP and AOPP, iPTH, Hey,β2-MG, AGE, IL-8, IL-18, CysC was positively related to its r=0.827,0.822,0.709,0.699,0.533,0.768,0.886,0.520,P less than 0.05;CRP and Kt/V showed no negative correlation, the r=-0.327, P=0.159; CRP was negatively correlated with Alb, which r=-0.730, P=0.000.3m, CRP and AOPP, iPTH, Hey, (32-MG, AGE, IL-8, IL-18, CysC was positively related to its r=0.758,0.704,0.762,0.800,0.549,0.919,0.939,0.640, P are is less than 0.05; CRP and Kt/V showed no correlation, its r=-0.095, P=0.689; CRP was negatively correlated with Alb, its r=-0.731, P=0.000.6m, plus HP treatment, CRP and AOPP, iPTH, Hcy,β2-MG, AGE, IL-8, CysC was positively related to its r=0.775,0.737,0.751,0.609,0.557,0.515,0.423, P are small was 0.05; CRP and Kt/V showed no correlation, the r=-0.272, P=0.245; CRP showed no correlation with the Alb and its r=-0.297, P=0.204.Conclusion:1.Plus with HP can get rid of part of the middle molecular toxins in maintenance hemodialysis patients's body,thus improving the micro-inflammatory state;2.Part of middle molecular uremic toxins(β2-MG,IL-8) involved in the inflammatory response;3.HP treatment can improve the level of Alb important reason may be related to micro-inflammatory state of improvement;4. To show there are obvious advantages on plasma clearance of middle molecular toxins in Uremic plasma in long-term sustained HP therapy, May need to expand the sample size or extension of observation time for further study.