HEMODIALYSIS

It was intended to examine the properties of cellulosic and synthetic artificial kidney membranes in relation to hemodialysis and find out the changes in the materials features and performances after the treatment. Therefore, it was purposed to make recommendations about the appraisal of reusable or disposable membranes by means of comparative analyses. This study fulfilled the gap in the literature via its interdisciplinary approach by incorporating totally original approaches, the brand new results and novel experiments and clinical analyses that ascertain and resolve some of the disputed recent biocompatibility issues and questions related to dialysis via comparatively indicating the correlation between the complex reaction of the biological system with the treatment environment and the physical, chemical, thermal, mechanical, morphologic and transport properties of the membranes. The impacts of the first use on membranes were reported for the first time in this thesis. The data of the study revealed that membrane type, hematocrit level, pump speed, biostability, molecular and supramolecular structure of various dialysers can be as important as mere membrane-blood interaction in hemocompatibility.
By conducting Kt/V calculations and Statistical Analyses (ANOVA, Taguchi) on the selected patients, it was elucidated that the impact of the inevitable direct interactions among the chosen eight factors (dialysis age, dialyzer membrane material, hematocrit, interdialytic weight difference, dialysate type, pump speed, heparin type, socioeconomic status) on the treatment adequacy was more potent than that of the individual ones. The data acquisition from the patients with end-stage renal failure and measurement of the Kt/V values based on Daugirdas-2 formula were achieved through database software. As hypothesized in the construction of the linear graph, it was concluded that membrane type is the most effective individual component (F=11.96) among the predetermined eight factors on the treatment adequacy and patient well-being and that the performance of the polysulfone in the treatment is higher than that of cellulosic membranes. Consequently, the difference between cellulosic (two Hemophan and Cellulose Acetate and one kind of Cuprophan) and synthetic (Polysulfone) membranes were probed in terms of their physical and chemical properties, molecular and supramolecular structures (semi-crystalline or amorphous), mechanical behaviors, surface topography and morphologies (porous or dense). By realizing the changes in the membranes that occur due to single use, the appropriateness of reuse of membranes in some countries in the absence of standards was also questioned. To these ends, mechanical (simple tensile tests, stress relaxation experiments, load-unload tests, sudden strain rate change experiments), morphological (Scanning Electron Microscope: SEM, Atomic Force Microscope: AFM, optic and stereo microscopes), chemical (Electron Dispersive X-Ray Spectroscopy: EDXS, Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy: ATR-FTIR, Crosspolarization Magic Angle Spinning Solid State Nuclear Magnetic Resonance Spectroscopy: SSNMR), thermal (Differential Scanning Calorimetry: DSC, Thermogravimetric Analysis: TGA) and physical (Positron Annihilation Lifetime Spectroscopy: PALS, X-Ray Diffraction: XRD) tests were conducted on both used and virgin membranes. SSNMR indicated the change in the supramolecular structure; formation of crosslinking and chain scissioning and the mobility decrease in the cellulosic membranes after utilization. According to the results of NMR and PALS, utilized polysulfone can be statistically accepted equal to the unutilized one. According to the results of PALS pertaining to Cellulose Acetate it was verified that following utilization the membrane is exposed to both severe physical and chemical ageing due to constant t3 with the greatest variation in the I3 parameter. Although SSNMR indicated that both used hemophan and cuprophan retain their before-use chemical properties, through PALS it was unearthed that hemophan which reveals greater reduction in I3 is influenced more than cuprophan after use. The ATR-FTIR Spectroscopy documented that after use, while polysulfone maintains the same functional groups, amide is incorporated into cellulosic membranes. By FTIR it was proved that polysulfone is the least impaired membrane after use. After use, contrary to polysulfone, SSNMR verified moderate chemical and physical ageing in cuprophan and hemophan, and severe ageing in cellulose acetate but variation in the type and amount of crystallinity and mobility decrease in cuprophan, hemophan and cellulose acetate. The crystalline structures of the membranes were detailed by fibers’ XRD. The XRD diffractograms of the unused membranes mostly showed both sharp peak features corresponding to regions of 3D order and more diffuse patterns characteristic of molecularly disordered structures. It was revealed that atomic structure of the virgin cellulosic membranes has small-molecule impurities at the atomic or molecular level that locally strain the crystal structure appeared as well-defined broad peaks. Following use, in XRD patterns, polysulfone did not indicate a crucial difference in terms of type and amount of crystallinity and molecular distortions while the number of defects in cellulosic membranes were increased dramatically enough to saturate the structure and decreased local variation of local lattice spacing and this, in turn, reduced peak width proving change in the crystallinity. XRD concluded that percentage of crystalline and amorphous portions was impaired due to use and transport capacity of the cellulosic membranes deteriorated even after single use since diffusion takes place in the amorphous regions and their crystalline interfaces.
Decreases in tensile strength, strain/fracture values, toughness and increase in strain hardening were identified in the used membranes excluding polysulfone. Virgin membranes exhibited ductile failure, hard and tough plastic behaviour whereas their used ones failing at much shorter times and much lower loads showed brittle failure and weak profile except polysulfone that is tough in both conditions. Decreased molecular free volume, increased packing (physical ageing), and impurities in the used cellulosic membranes obviously resulted in reduced molecular mobility leading ductile to brittle transition. By DSC and TGA, virgin cellulosic membranes commenced degrading at lower temperatures as compared with used ones. SEM studies on the virgin cellulosic fibers showed dense, symmetric, homogeneous structure and rough fracture surface compatible with ductile mode of failure. However, in used cellulosic membranes, fractography presenting smooth surface accompanied by large tearings and discontinuities testified embrittlement and ageing. Cellulosic membranes becoming brittle after one-use should be expected to be more prone to develop cracks and fracture, thus complications including rupture and backtransport associated with the passage of contaminants from dialysate to blood in multiple uses. Pore geometry and distribution, surface topography and roughness of the membranes were detailed by AFM. Fractography of polysulfone exhibited asymmetric, dual-skinned, porous and ductile structure.
It is required to reduce the cost of dialysis since, due to an increase in the mean age of the general population, there will be a progressive increase in dialysis patient numbers with comorbidity most of who will not be suitable for renal transplantation. However, it is well recommended that polysulfone, which yields the best results in terms of performance and the preservation of material properties, should be prefered to cellulosic membranes as both reusable and disposable membrane. Since this study proved that even first use deteriorates the properties, quality and transport capacity of membranes, reuse should only be taken into agenda as long as reliable analyses on the candidate membranes are performed in advance. Otherwise, disposable use of the membranes is recommended