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The projected future demand for renal replacement therapies for patients with end-stage renal failure requires preparedness at different levels. The deliberations focus predominantly on the disproportionately high financial burden of care for patients on routine dialysis therapy compared with other chronic conditions. However, even today there are concerns regarding the shortage of healthcare workers in the field of nephrology. A substantial increase in trained healthcare professionals is needed for the future delivery and care of patients requiring haemodialysis (HD) that 89% of patients on dialysis receive; a sustainable health workforce is the cornerstone of any healthcare system. The multimorbid nature of chronic kidney disease as well as the complexity—especially the technical aspects—of HD are deterrents for pursuing nephrology as a career. An educational platform that critically examines the essential issues and components of HD therapy was thus considered appropriate to create or renew interest in nephrology. By providing broader and newer perspectives of some of the core principles around which HD evolves, with this set of articles we seek to facilitate a better appreciation of HD. We believe that such a reappraisal of either poorly understood or ill-defined principles, including usage of terminology that is imprecise, will help facilitate a better understanding of the functioning principles of HD. [ABSTRACT FROM AUTHOR]

Blood-incompatibility is an inevitability of all blood-contacting device applications and therapies, including haemodialysis (HD). Blood leaving the environment of blood vessels and the protection of the endothelium is confronted with several stimuli of the extracorporeal circuit (ECC), triggering the activation of blood cells and various biochemical pathways of plasma. Prevention of blood coagulation, a major obstacle that needed to be overcome to make HD possible, remains an issue to contend with. While anticoagulation (mainly with heparin) successfully prevents clotting within the ECC to allow removal of uraemic toxins across the dialysis membrane wall, it is far from ideal, triggering heparin-induced thrombocytopenia in some instances. Soluble fibrin can form even in the presence of heparin and depending on the constitution of the patient and activation of platelets, could result in physical clots within the ECC (e.g. bubble trap chamber) and, together with other plasma and coagulation proteins, result in increased adsorption of proteins on the membrane surface. The buildup of this secondary membrane layer impairs the transport properties of the membrane to reduce the clearance of uraemic toxins. Activation of complement system-dependent immune response pathways leads to leukopenia, formation of platelet–neutrophil complexes and expression of tissue factor contributing to thrombotic processes and a procoagulant state, respectively. Complement activation also promotes recruitment and activation of leukocytes resulting in oxidative burst and release of pro-inflammatory cytokines and chemokines, thereby worsening the elevated underlying inflammation and oxidative stress condition of chronic kidney disease patients. Restricting all forms of blood-incompatibility, including potential contamination of dialysis fluid with endotoxins leading to inflammation, during HD therapies is thus still a major target towards more blood-compatible and safer dialysis to improve patient outcomes. We describe the mechanisms of various activation pathways during the interaction between blood and components of the ECC and describe approaches to mitigate the effects of these adverse interactions. The opportunities to develop improved dialysis membranes as well as implementation strategies with less potential for undesired biological reactions are discussed. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the biocompatibility profile of a newly developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class of dialyzers incorporates a number of novel design features (including a new membrane) that have been developed specifically in order to enhance the removal of small- and middle-size molecules. The new FX dialyzer series was compared with the classical routinely used high-flux polysulfone F series of dialyzers. In an open prospective, randomized, crossover clinical study, concentrations of the C5a complement component, and leukocyte count in blood and various thrombogenicity parameters were evaluated before, and at 15 and 60 min of hemodialysis at both dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S dialyzers and, after crossover, the classical F60S, while in another 9 patients, the evaluation was made with the dialyzers used in reverse order. The comparison of dialyzers based on evaluation of the group including all procedures with the FX60S and the group including procedures with the F60S did not reveal significant differences in platelet count, activated partial thromboplastin times, plasma heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point of the collecting period. Both dialyzer types showed a significant increase in the plasma levels of the thrombin-antithrombin III complexes; however, the measured levels were only slightly elevated compared with the upper end of the normal range. Biocompatibility parameters reflecting the behavior of platelets, fibrinolysis, complement activation, and leukopenia do not differ during dialysis with either the FX60S or the F60S despite their large differences in design and geometry features. Although coagulation activation, as evaluated by one of the parameters used, was slightly higher with the FX60S, it was still within the range seen with other highly biocompatible dialyzers and therefore is not indicative of any appreciable activation of the coagulation system. Thus, the incorporation of various performance-enhancing design features into the new FX class of dialyzers does not result in a deterioration of their biocompatibility profile, which is comparable to that of the classical F series of dialyzers. [ABSTRACT FROM AUTHOR]