| Background:In the recent decade, the prevalence of chronic kidney disease (Kidney Disease Chronic, CKD) has continued to grow in the world. In 2007-2010, the prevalence of CKD in adults in the United States has risen to 14%. In our country, Zhang Lu xia found that the revalcence rate of chronic kidney disease in Chinese adult had reached about 10.8% in 2012, according to the investigation of Shanghai Pudong New Area, Guangxi urban area, it shows the prevalence of CKD in adults reached about 11% and 14.4% respectively, and the CKD has become one of the common diseases in our country. But if the CKD patients failed to receive timely and effective treatment, and ultimately to end-stage renal disease requiring dialysis or transplantation treatment, not only the quality of life of patients decreased significantly, with the social labor ability have been greatly affected, and the treatment of CKD needs high medical costs, and will cause heavy economic burden for individuals and country.CKD patients also increase the risk of cardiovascular disease, cardiovascular disease (disease cardiovascular, CVD) is one of the major complications of CKD patients and one of the main causes of death. Especially when the CKD continues to progress into uremia, the end stage renal disease (ESRD) stage, CVD mortality accounts for ESRD of the total mortality rate of 45%-50%, its mortality rate is 10-20 times higher than the general population. Uremic cardiomyopathy is the leading cause of death in patients with end-stage renal disease (ESRD), especially in dialysis patients. The most prominent characteristic of CKD is left ventricular hypertrophy (LVH). LVH is an independent risk factor for the reduction of survival rate of ESRD and dialysis patients, and the pathogenic factors are complicated.LVH will be appeared in the early and middle period of CKD, the incidence rate of dialysis patients has been as high as 74%, and has become an important pathological basis of ventricular diastolic dysfunction, arrhythmia and heart failure. It was previously believed that the occurrence of LVH in uremic patients was mainly related to hypertension and high capacity load, but the control of blood pressure and volume load could not be significantly improved LVH. In uremic patients with secondary parathyroid hormone, calcium and phosphorus metabolism disorder and oxidative stress, and other microinflammatory state also has the potential to promote the occurrence of LVH. Microinflammatory state is one of the important factors.Research shows that LVH is closely related to the microinflammatory state, and macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine in micro inflammatory state, up-regulated expression of MIF-173CC genotype in ESRD patients with inflammatory markers of microinflammatory state is directly related toe the level of in serum high sensitivity C reactive protein (hs-CRP). In the study of autoimmune giant cell myocarditis, it was found that the disease was significantly reduced after injection of MIF neutralizing antibody. It is hypothesized that the role of MIF in the treatment of uremic patients may reduce the degree of the disease, and may be a new direction for the treatment of uremic cardiomyopathy, but there is no relevant research.Objective:This study was designed to test the subjects by the level of serum macrophage migration inhibitory factor (MIF), inflammatory markers (high sensitive C-reactive protein (hs-CRP)) in end-stage renal disease (ESRD) patients; to explore the role of level of serum MIF and hs-CRP in microinflammation, to approach the correlation between MIF, high sensitive C-reactive protein (hs-CRP) and left ventricular hypertrophy (LVH) in patients with ESRD. The results will provide evidence and a new theoretical basis for the prevention and treatment in ESRD patients with LVH.Methods:1. We selected 144 cases of end-stage renal disease that were recruited in Department of Renal medicine, the central hospital of Qingdao and Taian between October 2014 and August 2015 for the study group, and 30 healthy subjects as control group. All of the patients were in accordance to the inclusion and exclusion criteria. The patients were divided into three groups according to the dialysis situation:Non dialysis of ESRD group (ND group, n=63), hematodialysis group (HD group, n=51), peritoneal dialysis group (PD group, n=30), patients with hemodialysis group were low flux hemodialysis.2.Detection index:(1) Collection of clinical data, all data include age, sex, blood pressure and etc. At the same in the central hospital of Qingdao and Taian, we used SYSMEX XE2100 hematology analyzers and ancillary reagents to count the red blood cell and hemoglobin. (2) In the central hospital of Qingdao and Taian, we used immunonephelometry, which was proceeded by Roche automatic electrochemilumin-escence immunoassay analyzer (ROCHE COBAS 8000) and ROCHE supporting reagents for testing in strict accordance with the conventional steps, to detect serum concentrations of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), apolipoprotein A (APOA), apolipoprotein B (APOB), lipoprotein (a) (LP(a)), Prealbumin (PA), albumin (ALB), potassium (K+), sodium chloride (Na+), chloridion (Cl-), calcium (Ca2+), magnesium (Mg2+), phosphate (P3+), urea nitrogen (BUN), Creatinine (Cr), uric acid (UA), beta 2-microglobulin (beta 2-MG), cystatin C (CysC), and the levels of serum hs-CRP in different groups, normal value of hs-CRP was less than 3mg/L; (3) In the Kidney transplant immunology laboratory in Peking University Third Hospital, we used Bio-Plex cytokine assay (Bio-Plex suspension protein chip system, our test was conducted with Bio-Plex human cytokinemulti-plex kit and Bio-Plex cytokine reagent kit of Bio-Rad in USA), which could detect simultaneously a variety of cytokines in the same specimen, to detect the levels of MIF in different groups. The reaction occurred on the encoded microspheres of different fluorescent, which included antigen and antibody, ligand and receptor, enzyme and substrate, nucleic acid hybridization reaction. The instrument respectively detected coding and reporter fluorescent microspheres to achieve the purpose of the qualitative and quantitative through red and green laser beams. The procedure of Luminex detection cytokines was divided into three steps:step 1:Probe molecules fixed; Step 2: detection reaction; step 3:laser analysis. The data analysis application was Bio-Plex Manager software (version 4.0), its sensitivity was less than 10 pg/mL. The concentration of cytokines could be determined accurately by this method with a range of 1-32000pg/mL. (4)ultrasound system:left ventricular end diastolic dimension (LVDD), interventricular septum thickness (IVST), left ventricular ejection fraction (LVEF%) and left ventricular posterior wall thickness (LVPWT) were measured using the IU22 ultrasound system (Philips Medical Systems, Bothell, WA, United States of America). All measurements were performed by an experienced ultrasound doctor, with a mean value of three times. Left ventricular mass (LVM) was calculated using the ASE-recommended formula LVM=0.8{ 1.04×[(LVDD+IVST+LVPWT)3-LVDD3]} +0.6, and was indexed for the body surface area (LVMI). LVH was defined by LVMI>134g/m2in male subjects and>110g/m2 in female subjects. Subjects were divided into a hypertrophy group and a non-hypertrophy group. Uremic cardiomyop-athy was defined according to previously published standards.3.Statistical analysis was performed using SPSS for Windows version 21.0 (SPSS, Inc., Chicago, IL, USA). Results were expressed as mean and standard deviation (SD; normally distributed variables) or median and range (non-normal distribution) unless otherwise indicated. As the MIF and hs-CRP data were not normally distributed, the Kruskal-Wallis Test was used to analyse potential statistical significance across different groups, and between healthy subject groups and patient groups. Spearman’s rank correlation test was used to measure associations among continuous and ordinal variables. In addition, logistic regression analysis was performed to determine relative risk. A p value<0.05 was regarded as statistically significant.Results:1.There were 144 selected patients with ESRD in total, including 80 male (55.6%), and 64 female (44.4%). The age was between 19 years to 86 years, and the average age was 55.3 ± 15.9 years.30 sex and age-matched healthy Chinese volunteers were recruited as normal controls. According to the dialysis situation, Non dialysis of ESRD group, hematodialysis group, peritoneal dialysis group. There was no significant difference in age and sex among the three groups. In these three groups, the main causes of chronic kidney disease in patients with chronic glomerulonephritis and hypertensive renal damage.2.MIF and hs-CRP in serum ESRD level:After Kruskal-Wallis test, the results showed that the three groups treatment group had statistical significance of MIF (p<0.05) compared with the control group, and comparing between the three groups showed end-stage renal disease in non dialysis group, hemodialysis and peritoneal dialysis group and serum MIF compared with statistical significance the level of MIF significantly (p<0.05). After Kruskal-Wallis test, we found that the level of hs-CRP of end-stage renal disease in non hemodialysis group, peritoneal dialysis group, hemodialysis group compared with healthy control group, the difference was statistically significant (p<0.05), but not dialysis group of ESRD group, hemodialysis and peritoneal dialysis group, between two comparison,there was no significant difference of hs-CRP (p>0.05).3.Correlation of serum migration inhibitory factor and clinical characteristics in chronic kidney disease patients was showed as follows:Spearman rank correlations for macrophage migration inhibitory factor in ESRD patients,we found the serum MIF levels were not correlated with systolic blood pressure, diastolic blood pressure, number of red blood cells, total cholesterol, triglyceride, apolipoprotein A, apolipoprotein B, sodium, chloridion, calcium, magnesium, phosphate, creatinine, uric acid, beta2-microglobulin, cystatin C, left ventricular end diastolic dimension, interventricular septum thickness, left ventricular posterior wall thickness and left ventricular ejection fraction (P>0.05). The serum MIF levels were correlated positively with serum hs-CRP, potassium, and urea nitrogen (p<0.05). The serum MIF levels were negatively correlated with albumin, hemoglobin (p<0.05). 4.The relationgship between serum MIF level and left ventricular hypertrophy: according to the results of cardiac Doppler ultrasound, and ESRD patients were divided into hypertrophy group and nonhypertrophy group. MIF was associated with LVMI with a concentration of 1186.0 (170.0-3862.0) pg/mL for hypertrophy group and 228.5 (55.0-2079.0) pg/mL for nonhypertrophy group. Logistical correlation analysis was carried out to examine the RR of MIF to LVH. An MIF>1100 pg/mL was defined as abnormal while an MIF≤1100 pg/mL was defined as normal. Logistic regression analysis was performed to determine relative risk (RR)When consideringOR, LVH is 13.063 times more likely to occur in patients with increased serum MIF than a low serum MIF.Conclusions:l.The serum levels of MIF and hs-CRP were significantly increased in patients with end-stage renal disease (ESRD), which showed that ESRD patients had high MIF and micro inflammatory status.2.The serum levels of MIF and hs-CRP in patients with end-stage renal disease (ESRD) may be involved in the occurrence and development of left ventricular hypertrophy in ESRD patients.3. High serum MIF levels can be considered as a risk factor for left ventricular hypertrophy in patients with ESRD. Blocking MIF in the body of uremic patients may reduce the disease in uremic cardiomyopathy, which provides a clinical basis and theoretical basis for the treatment of uremic cardiomyopathy. |
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