Study of Relationship between Endotoxemia and Cardiovascular Disease in Hemodialysis Patients

Abstract

It has been reported that there were gradated increases in endotoxemia with increasing CKD stage andserum endotoxin levels were nearly six times higher in CKD patients receiving maintenance dialysis compared with those without dialysis(Mcintyre et al., 2011). Exposure to high levels of endotoxin is clearly associated with short-term complications ranging from pyrogenic reactions to septicemia. In addition, long-term endotoxin challenge promotes a state of chronic inflammation with subsequent frequent complications in HD patients (Terawaki et al., 2010). It has been evidenced that endotoxemia results in a broad range of negative cardiovascular effects and may explain in part the markedly increased cardiovascular death rate in HD patients (Neves et al., 2013). We aimed at this study to determine the relative contribution of endotoxemia to cardiovascular diseasesassessed by echocardiography and carotid artery dopplerinthe prevalent HD patients. This cross sectional study was taking place in Ain Shams University Hospitals. 40 patients on prevalent HD were randomly selected to participate in this study including 27 (67.50%) males and 13 (32.50%) females. The mean age was 47.97±14.42 years and the mean duration of HD was 78.15 ± 65.30 months. Measurements of endotoxin levels in (dialysate, bicarbonate concentrate, before RO water and after RO water) were done using an ELISA test and values were estimated to be (0.12, 0.35, 0.40, 0.10) Eu/mL respectively. Endotoxin level in dialysate water in our study meets the current recommendations of the Association for the Advancement of Medical Instrumentation (AAMI); which endorses a maximal allowable limit of endotoxin concentration <0.25 EU/ml indialysis water and<0.5 EU/ml in the dialysate. In contrast, ultrapure dialysate, commonly used in Europe but not widely in the United States has an endotoxin level threshold of <0.03 EU/mL (Coulliette and Arduino, 2013). Blood samples were collected before and after the mid-week HD session to determine pre-dialysis and post-dialysis serum endotoxin levels.In addition, delta change of serum endotoxin level was calculated as: delta change of endotoxin= (pre-dialysis endotoxin) – (post-dialysis endotoxin). The mean pre-dialysis endotoxin level was 0.356 ± 0.090 Eu/mL and the mean post-dialysis endotoxin level was 0.367 ± 0.110 Eu/mL.16 (40%) patients showed no change in the serum endotoxin level after the HD session. Meanwhile, 12 (30%) patients showed an increase in the serum endotoxin level after the HD session and 12 (30%) patients showed a decrease in the serum endotoxin level after the HD session. In a comparison between the studied groups, there was a significant difference between the 3 groups regarding the age (P= 0.041) and serum iron level (P= 0.030). In addition, our study showed a significant correlation between delta change of the serum endotoxin level and serum K level (P= 0.004), and a significant correlation between the age and post-dialysis endotoxin level (P= 0.02). Our study showed a significant negative correlation between pre-dialysis endotoxin level and serum albumin level (r= -0.38, P=0.01). We didn’t confirm a significant correlation between post-dialysis endotoxin level and ultrafiltration volume. In a similar context, our study didn’t confirm a significant correlation between duration of HD therapy and serum endotoxin level. Our study showed a significant correlation between delta change of serum endotoxin level and the late trans-mitral diastolic velocity (MV A vel) (P= 0.02).In addition,there was a significant correlation between post-dialysis endotoxin level and both early/ late trans-mitral diastolic velocities (MV E/A ratio) (P= 0.03) and LV diastolic dysfunction (P= 0.04). Our study showed a significant negative correlation between delta change of serum endotoxin level and EF% (r= -0.36, P= 0.02), and a significant correlation between delta change of serum endotoxin level andLV end-systolic diameter (LVESD)(P= 0.02). In our study, in a linear regression multivariate analysis for factors affecting endotoxin delta change, there was a significant correlation with both MV A vel and serum K level. In a linear regression univariate analysis for factors affecting MVE/A ratio, there was a significant correlation between post-dialysis endotoxin and MV E/A ratio. However, in a linear regression multivariate analysis for factors affecting MV E/A ratio, none of the studied factors including: age, HGB, PTH, cholesterol, HDL, LDL, TG, pre-dialysis endotoxin and post-dialysis endotoxin had a significant independent effect on MV E/A ratio. Carotid artery doppler examination was done to assess both carotid arteriesintima-media thickness (cIMT), having atheromatous plaques and or stenosis. (cIMT≥ 1mm) was considered as significant atherosclerosis (Najafian et al., 2008), and stenotic lesion over 50% of the cross sectional surface was defined as significant stenosis (Chambers and Donnan,2005). The meancIMTwas 0.093± 0.0313 cm.26 (65%) patients had no atherosclerotic changes while 14 (35%) were shown to have. 37 (92.5%) patients had no stenotic lesions, 2 (5.0%) had a non-significant stenosis and only one patient had a significant stenosis. Our study showed a significant correlation between post-dialysis endotoxin level and CCA atherosclerotic changes (P= 0.048).