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Informed decision-making is paramount to the improvement of dialysis therapies and patient outcomes. A cornerstone of delivery of optimal dialysis therapy is to delineate which substances (uraemic retention solutes or 'uraemic toxins') contribute to the condition of uraemia in terms of deleterious biochemical effects they may exert. Thereafter, decisions can be made as to which of the accumulated compounds need to be targeted for removal and by which strategies. For haemodialysis (HD), the non-selectivity of membranes is sometimes considered a limitation. Yet, considering that dozens of substances with potential toxicity need to be eliminated, and targeting removal of individual toxins explicitly is not recommended, current dialysis membranes enable elimination of several molecules of a broad size range within a single therapy session. However, because HD solute removal is based on size-exclusion principles, i.e. the size of the substances to be removed relative to the mean size of the 'pores' of the membrane, only a limited degree of selectivity of removal is possible. Removal of unwanted substances during HD needs to be weighed against the unavoidable loss of substances that are recognized to be necessary for bodily functions and physiology. In striving to improve the efficiency of HD by increasing the porosity of membranes, there is a greater potential for the loss of substances that are of benefit. Based on this elementary trade-off and availability of recent guidance on the relative toxicity of substances retained in uraemia, we propose a new evidence-linked uraemic toxin elimination (ELUTE) approach whereby only those clusters of substances for which there is a sufficient body of evidence linking them to deleterious biological effects need to be targeted for removal. Our approach involves correlating the physical properties of retention solutes (deemed to express toxicity) with key determinants of membranes and separation processes. Our analysis revealed that in attempting to remove the relatively small number of 'larger' substances graded as having only moderate toxicity, uncontrolled (and efficient) removal of several useful compounds would take place simultaneously and may compromise the well-being or outcomes of patients. The bulk of the uraemic toxin load comprises uraemic toxins below <30 000 Da and are adequately removed by standard membranes. Further, removal of a few difficult-to-remove-by-dialysis (protein-bound) compounds that express toxicity cannot be achieved by manipulation of pore size alone. The trade-off between the benefits of effective removal of the bulk of the uraemic toxin load and risks (increased loss of useful substances) associated with targeting the removal of a few larger substances in 'high-efficiency' HD treatment strategies needs to be recognized and better understood. The removability during HD of substances, be they toxic, inert or beneficial, needs be revised to establish the pros and cons of current dialytic elimination strategies. [ABSTRACT FROM AUTHOR]

In most biological or industrial (including medical) separation processes, a membrane is a semipermeable barrier that allows or achieves selective transport between given compartments. In haemodialysis (HD), the semipermeable membrane is in a tubular geometry in the form of miniscule pipes (hollow fibres) and separation processes between compartments involve a complex array of scientific principles and factors that influence the quality of therapy a patient receives. Several conditions need to be met to accomplish the selective and desired removal of substances from blood in the inner cavity (lumen) of the hollow fibres and across the membrane wall into the larger open space surrounding each fibre. Current HD membranes have evolved and improved beyond measure from the experimental membranes available in the early developmental periods of dialysis. Today, the key functional determinants of dialysis membranes have been identified both in terms of their potential to remove uraemic retention solutes (termed 'uraemic toxins') as well subsidiary criteria they must additionally fulfill to avoid undesirable patient reactions or to ensure safety. The production of hundreds of millions of kilometres of hollow fibre membranes is truly a technological achievement to marvel, particularly in ensuring that the fibre dimensions of wall thickness and inner lumen diameter and controlled porosity—all so vital to core solute removal and detoxification functions of dialysis—are maintained for every centimetre length of the fragile fibres. Production of membranes will increase in parallel with the increase in the number of chronic kidney disease (CKD) patients expected to require HD therapies in the future. The provision of high-quality care entails detailed consideration of all aspects of dialysis membranes, as quality cannot in any way be compromised for the life-sustaining—like the natural membranes within all living organisms—function artificial dialysis membranes serve. [ABSTRACT FROM AUTHOR]

The majority of patients with chronic kidney disease are currently treated with dialyzers containing synthetic membranes. Of all the dialysis membranes made from these polymers, 93% are from the parent polyarylsulfone family of which 71% are from polysulfone (PSu) and 22% from polyethersulfone. The preference of nephrologists for PSu dialyzers signifies their versatility in terms of meeting the solute and fluid removal demands for all treatment modalities (low-and high-flux dialysis, online hemodiafiltration, hemofiltration). The unprecedented success and widespread usage of PSu membranes is attributed, in addition to efficient removal of a broad spectrum of uremic toxins, to other criteria required of modern dialysis therapies. Namely, effective endotoxin retention capacity, pronounced intrinsic biocompatibility and low cytotoxicity are factors which all contribute to minimal adverse clinical sequelae. Furthermore, PSu by virtue of its high thermal stability can be sterilized with steam, the preferred mode of sterilization as it does not have the disadvantages associated with other sterilization methods. However, there are significant differences between membranes made from PSu due to differences in membrane polymer recipes and manufacturing technologies. Although PSu may be the main constituent, these membranes are blended with other polymers, e.g. hydrophilizing agents, such as polyvinylpyrrolidone to give each membrane its characteristic profile. The relative amounts of the two (or more) co-polymers as well as the spinning conditions provide a fingerprint of each membrane in terms of solute separation characteristics, biocompatibility, cytotoxicity or endotoxin retention capabilities. PSu membrane-based dialyzers thus fulfill the crucial therapy requirements of current treatment modalities to varying extents. Thereby, different effects towards patient outcomes and treatment safety are achieved., (Copyright © 2011 S. Karger AG, Basel.)

There is widespread recognition that the poor survival rates of dialysis patients, attributed predominantly to cardiovascular disease, need to be addressed and improved. In this paper, we relate diverse aspects of modern dialysis technology with factors that are considered to contribute towards increased mortality and morbidity in the dialysis population. Firstly, we assess the overall cardiovascular burden of the dialysis patient: it is the sum of uraemia-related risk factors (URRF), traditional risk factors and dialysis-therapy-related factors. Secondly, we describe how key components of the dialysis procedure may be directly related to the more common URRF: the dialyser and the membrane, microbiological quality of water and dialysate, treatment modality and online monitory equipment. The judicious selection and application of these components may collectively help improve patient outcomes in hemodialysis therapy.