UNRESOLVED ISSUES IN DIALYSIS: Ultrapure Dialysate: Facts and Myths

Abstract

During hemodialysis, blood comes in contact with a large volume of dialysate. Since the purity of dialysate has been linked to acute and long-term complications in hemodialysis patients, the limit of bacterial and endotoxin contamination has been reduced in recent years. Questions have been raised as to whether ultrapure dialysate is required to prevent such complications; in particular, the chronic inflammatory status frequently found in chronically hemodialyzed patients. In vivo and in vitro data suggest that cytokine stimulation in the blood depends on the concentration of bacteria or endotoxin in the dialysate and on the endotoxin permeability of the dialysis membrane. It is not proven whether ultrapure dialysate reduces significantly proinflammatory cytokine generation compared with standard dialysate within the limits of recent recommendations, if rather impermeable dialysis membranes are used. Cuprophane membranes are more permeable to cytokine-inducing substances compared with synthetic membranes such as polysulfone and polyamide. Clinical reports have also attempted to link several acute and chronic complications of hemodialysis to dialysate purity. To date, however, there is no large randomized clinical trial demonstrating that ultrapure dialysate significantly reduces biomarkers of inflammation and other consequential putative complications, including dialysis-related amyloidosis, erythropoietin requirement, and cardiovascular morbidity and mortality. In conclusion, based on the existing clinical data, ultrapure dialysate is recommended in the setting of suboptimal bacteriologic quality of standard dialysate and the use of permeable dialysis membranes.

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

“…In recent years, the maximum limit of bacterial and endotoxin contamination in dialysate has been reduced. For the currently recommended ultrapure dialysate, the Association for the Advancement of Medical Instrumentation introduced a bacterial count limit of less than 0.1 CFU/ml and an endotoxin level of less than 0.03 EU/ml, which is identical to the detection limit provided by the commonly used Limulus amebocyte lysate assay [13]. The use of an ultrapure dialysate results in a reduction in dialysate endotoxin level, and is reported to reduce inflammatory responses in hemodialysis patients, such as the increase in plasma levels of C-reactive protein (CRP), interleukin-6, and β 2 -microglobulin [14,15,16,17].…”

Impact of Low- or High-Flux Haemodialysis and Online Haemodiafiltration on Inflammatory Markers and Lipid Profile in Chronic Haemodialysis Patients

“…On the other hand, switching from low- to high-flux membranes with a larger pore size may increase the transfer of endotoxin and its fragments during routine high-flux HD via backfiltration, which may contribute to enhanced cytokine induction. These factors together may explain the observation of similar effects of low- and high-flux polysulphone membranes on the inflammatory mediators in our study [13]. …”

Effects of Different Levels of Endotoxin Contamination on Inflammatory Cytokine Production by Peripheral Blood Mononuclear Cells after High-Flux Hemodialysis

“…Although there are an increasing number of clinical studies [15,16,17,18] showing the impact of dialysate endotoxin contamination in high-flux HD on long-term HD-related complications, it is unknown which endotoxin contamination limit can minimize endotoxin exposure-related adverse effects [15,19]. Our study demonstrated that the quality of the dialysate is correlated with the levels of endotoxin contamination.…”