Effect of Using Ultrapure Dialysate for Hemodialysis on the Level of Circulating Bacterial Fragment in Renal Failure Patients

Abstract

Background: Cardiovascular disease is the major cause of mortality and morbidity in dialysis patients. Recently, circulating endotoxin is found to associate with the systemic inflammatory state and cardiovascular disease of dialysis patients. Previous studies showed that the use of ultrapure dialysate for hemodialysis could reduce the exposure to exogenous endotoxin. We studied the effect of using ultrapure dialysate for hemodialysis on circulating endotoxin and bacterial DNA fragment levels and vascular stiffness. Methods: This is an open-labeled prospective study of 25 patients (14 male). Circulating endotoxin and bacterial DNA level, vascular stiffness as represented by arterial pulse wave velocity (PWV), nutrition and hydration status were monitored before and repeatedly throughout 12 months after the use of ultrapure dialysate for hemodialysis. Results: The average age was 58.9 ± 10.2 years; 21 patients completed the study. Within 4 weeks of conversion to ultrapure dialysate for hemodialysis, the plasma endotoxin level fell from 0.302 ± 0.083 to 0.209 ± 0.044 EU/ml (p < 0.0001) and then remained static, while serum bacterial DNA level remained similar. Furthermore, the time-averaged plasma endotoxin level during the study period significantly correlated with serum C-reactive protein level (r = 0.483, p = 0.017), carotid-femoral PWV (r = 0.455, p = 0.033), and malnutrition inflammation score (r = 0.461, p = 0.031). The time-averaged serum bacterial DNA level significantly correlated with malnutrition inflammation score (r = 0.550, p = 0.008) and inversely with subjective global assessment score (r = -0.543, p = 0.009), but not with PWV. Conclusions: In hemodialysis patients, circulating endotoxin level is associated with vascular stiffness and systemic inflammation. Using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin level in hemodialysis patients. The long-term benefit of using ultrapure dialysate for hemodialysis requires further study.

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

“…76 In patients on hemodialysis, plasma endotoxin level fell by one third within 4 weeks of conversion to ultrapure dialysate. 77 In this study, the timeaveraged plasma endotoxin level correlated with serum CRP level, carotid-femoral PWV, and malnutrition inflammation score. 77 In essence, this study strongly supports the notion that circulating endotoxin has direct effects on systemic inflammatory state, and ultrapure dialysate is effective in reducing circulating endotoxin in patients on hemodialysis.…”

Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients

“…However, we are not aware of any treatment that could increase the clearance of circulating DNA fragments. We have previously showed that using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin but not bacterial DNA level in hemodialysis patients [43]. Further clinical trials in this area are much needed.…”

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

“…The presence of even slight amounts of bacterial endotoxins in the dialysate undermines the biocompatibility of HD therapy and may subsequently upregulate the formation of oxidative molecules . Several investigators suggested that HD with ultrapure dialysate may decrease plasma concentrations of inflammatory and OS markers and improve anemia . A meta‐analysis including 31 studies and 1580 patients on maintenance HD showed that treatment with ultrapure dialysate significantly suppressed OS and inflammation, as assessed by plasma levels of MPO, ox‐LDL, C‐reactive protein (CRP), and interleukin‐6 (IL‐6) .…”

“…39,40 Several investigators suggested that HD with ultrapure dialysate may decrease plasma concentrations of inflammatory and OS markers and improve anemia. [41][42][43][44][45][46][47] A meta-analysis including 31 studies and 1580 patients on maintenance HD showed that treatment with ultrapure dialysate significantly suppressed OS and inflammation, as assessed by plasma levels of MPO, ox-LDL, C-reactive protein (CRP), and interleukin-6 (IL-6) . 46 An ultrapure dialysate-based dialysis is relatively easy and inexpensive to achieve by using special dialysate filters.…”