Challenges and Advances in Hemodialysis Membranes

Hemodialysis (HD) is a filtration vital process through which the bloods’ toxins and contaminations are removed. However, several immune system activations occur during dialysis, which can result in morbidity and mortality. The efficiency of the currently available blood purification process is hindered, on one hand, by the deficient toxins and middle molecule removal, and on the other hand, with the loss of valuable blood components (such as plasma and its constituents). This chapter offers an overview of the challenges and advances in HD membranes. It includes an introduction of the end stage renal disease, concepts of dialysis, its historical background, and the path through which the configurations and materials evolved. The interactions between membrane polymeric materials with human blood is also discussed. The aspect of material modification is one of the critical areas in HD technology as it targets to solve the most immediate and prevalent HD issue of membrane bioincompatibility. High flux dialysis (HFD) and hemofiltration (HF) are introduced and discussed. This class of membranes was introduced to solve middle molecule (such as β2- microglobulin) related challenges. This chapter highlights the question of why the issue of incompatible materials still exists along with current membrane modifications

Attenuated Combined Action of Cyclosporine A and Hyperlipidemia on Atherogenesis in Rabbits by Thymoquinone

This descriptive study investigates in a rabbit model of atherosclerosis (i) the extent of atherogenesis induced by cyclosporine A (CsA) or hyperlipidemia alone or in combination and (ii) whether thymoquinone (TQ), a known herbal antioxidant, offers protection against these effects. New Zealand White female rabbits were assigned to five groups of six animals each: Group I, control; Group II, CsA [25 mg kg−1 day−1 orally (PO)]; Group III, 1% cholesterol; Group IV, 1% cholesterol + CsA (25 mg kg−1 day−1 PO); and Group V, 1% cholesterol + CsA (25 mg kg−1 day−1 PO) + TQ (10 mg kg−1 day−1 PO). Lipids and oxidative stress parameters [Malondialdehyde (MDA) and protein carbonyl] and aortic atherosclerosis were compared. CsA alone did not show a significant effect on either serum lipids and did not induce atherosclerosis. High-cholesterol diet induced atherosclerosis (45 ± 11% of the intimal surface of aorta was covered with atherosclerotic plaques). CsA and high-cholesterol diet increased atherosclerosis severity as measured from intimal and media lesions, but did not affect the extent of atherosclerosis. TQ decreased aortic MDA by 83%. It was also associated with reduced aortic atherosclerosis extend by 52% compared with Group IV. We concluded that (i) CsA aggravates hyperlipidemia-induced atherosclerosis and (ii) TQ attenuates the oxidative stress and atherogenesis induced by the combined effect of CsA and hyperlipidemia

Assessment of the Genotoxicity, Antigenotoxicity on Alloxan-Induce Diabetic in Mice by Micronuclus(MN) Assay

Fenugreek (Trigonellafoenum-graecum ) plant has become interest subject because of its beneficial effects on human health, good nutritive value in addition it has antigenotoxic  effects therefore, the purpose of the present study was to investigate antigenotoxic  effects of alcoholic extract of Fenugreek seed at 200 mg /kg b.w  on mice bone marrow which treatmed with alloxan, 6-mercaptopurine anticancer at 200 mg /kg b.w by using micronuclus test at 5 day for all treatments. Cytogenetic study showed significant increasing at (p< 0.05) in Micronuclus number  MN in diabetic mice, anticancergroup or both when compared to the negative control. After 5day of alloxan treated mice with marked hyperglycemia (blood glucose),results recorded significant increase at (p< 0.05) in diabetic group ( group treated with alloxan) than anticancer in same time compared with control. Finally, alcoholic extracts of  Fenugreek seeds found significant reduced MN, blood glucose in all treated groups. These results indicate that fenugreek plant were one of the primary supplements used to support type I diabetics or insulin-dependent diabetes mellitus (NIDDM), in addition  it has active compounds which have important role on antigenotoxic, hyperglycemia  activity. Keywords: Extracts,Fenugreek,Alloxan,Micronuclus assay ,anticancer,mercaptopurine

Validity of Cardiovascular Risk Prediction Models in Kidney Transplant Recipients

Background. Predicting cardiovascular risk is of great interest in renal transplant recipients since cardiovascular disease is the leading cause of mortality. Objective. To conduct a systematic review to assess the validity of cardiovascular risk prediction models in this population. Methods. Five databases were searched (MEDLINE, EMBASE, SCOPUS, CINAHL, and Web of Science) and cohort studies with at least one year of follow-up were included. Variables that described population characteristics, study design, and prognostic performance were extracted. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate bias. Results. Seven studies met the criteria for inclusion, of which, five investigated the Framingham risk score and three used a transplant-specific model. Sample sizes ranged from 344 to 23,575, and three studies lacked sufficient event rates to confidently reach conclusion. Four studies reported discrimination (as measured by c-statistic), which ranged from 0.701 to 0.75, while only one risk model was both internally and externally validated. Conclusion. The Framingham has underestimated cardiovascular events in renal transplant recipients, but these studies have not been robust. A risk prediction model has been externally validated at least on one occasion, but comprehensive validation in multiple cohorts and impact analysis are recommended before widespread clinical application is advocated

Education Before Kidney Transplantation: What Do Patients Need to Know?

Astellas Pharma Canada Inc.Peer ReviewedCONTEXT: Poor knowledge about immunosuppressive (IS) medications remains a major problem for patients in the posttransplant setting. Therefore, more effective educational strategies in the pretransplant setting are being considered as a possible method to improve knowledge and readiness for the challenges of posttransplant care. However, the most effective/relevant content of a pretransplant educational program is yet to be determined. OBJECTIVE: To identify pretransplant education topics from the posttransplant patient perspective. DESIGN: A focus group meeting was conducted among 7 high-functioning, stable adult kidney transplant recipients recruited from the Saskatchewan Transplant Program. Demographic information including age, gender, occupation, background/ethnicity, and time since transplant were recorded. A moderator, assistant moderator, and research assistant facilitated the 90-minute focus group meeting using a predetermined semistructured interview guide. The session was audio recorded and transcribed verbatim. Nvivo software was used to code the data and identify emerging themes exploring views of participants relating to the educational information required for pretransplant patients. RESULTS: Patients were satisfied with the education they had received. Ideas were classified into the following major themes-patient satisfaction, transplant waitlist, surgery, medications, posttransplant complications, lifestyle and monitoring, knowledge acquisition, illusion of control, and life changes posttransplant. Knowledge gaps were identified in all areas of the transplantation process and were not exclusive to IS medications. CONCLUSION: Misconceptions regarding transplantation were identified by a group of high-functioning, stable adult recipients who were satisfied with their clinical care. Future educational strategies should aim to address the entire transplantation process and not be limited to medications

cellular perspectives

Vitamin D plays an essential role in bone metabolism. The discovery that the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, is expressed in most tissues led researchers to investigate other biological actions of vitamin D. These effects were found to include anti-inflammatory effects and antiatherogenesis, decreased renin activity and biosynthesis, induction of cell differentiation, inhibition of cell growth, and immunomodulation. In spite of the plethora of evidence on the protective effects of vitamin D, the reports on its intoxication still are considerably few. Therefore, in this review we aim to summarize the molecular and cellular bases of the protective and toxic vitamin D actions that are mediated mostly by VDR. This review will also shed light on vitamin D metabolites other than the active metabolite calcitriol and particularly 25hydroxy vitamin D (25(OH)D), putting emphasis on its magnifying role in vitamin D intoxication. One of the important themes we discuss is defining serum levels of beneficial or toxic effects of other exogenous vitamin D administration and its impact on 25(OH)D serum levels in animals and human subjects

Contribution of diminished kidney transplant GFR to increased circulating chemokine ligand 27 level

Abstract Background Inflammatory chemokine ligands (CCLs) play an important role in cardiovascular disease and allograft injury. CCLs may independently associate with diminished estimated glomerular filtration rate (eGFR) in stable renal transplant recipients (RTR). Methods Plasma levels of 19 CCLs (1, 2, 3, 4, 5, 8, 11, 13, 15, 17, 21, 24, 26, 27, CXCL5, 8, 10, 12 and 13) were measured in a cohort of 101 RTR. The cohort was divided according to CKD-EPI equation into three groups; group 1: eGFR ≥ 60 ml/min, group 2: eGFR 30–59.9 ml/min and group 3 eGFR ≤ 29.9 ml/min. ANOVA, Krusklwallis, Mann- Whitney Spearman correlation and regression analysis tests were used to determine association between reduced eGFR and inflammatory CCLs plasma levels measured by multiplex techniques. 20 healthy subjects with eGFR above 90 ml/min were included as control. Significance was sat at < 0.05. Results Levels of CCLs 1, 4, 15, 27, CXCL8 and CXCL10 were significantly different among the four studied groups. Multivariate regression analysis (MVA) between eGFR and all CCLs demonstrated that CCL27 was the only ligand to remain significantly associated with diminished eGFR {P = 0.021 and r = − 0.35,(P = 0.001)}. In a second MVA between CCL 27 and patient’s demographics and laboratory variables, diminished eGFR, and elevated PTH, out of the twenty one available variables remained significantly associated with elevated CCL27levels. Conclusion Diminished eGFR in stable RTR is associated with elevated plasma levels of CCL27. This association may explain, at least in part, the independent contribution of reduced eGFR to enhanced inflammation in RTR

Quality of Life of Dialysis Patients: Exploring the Influence of Membrane Hemocompatibility and Dialysis Practices on Psychosocial and Physical Symptoms

Hemodialysis (HD) is a life-sustaining membrane-based therapy that is essential for managing kidney failure. However, it can have significant physical and psychological effects on patients due to chronic or acute consequences related to membrane bioincompatibility. End-stage renal disease (ESRD) patients on hemodialysis have a high incidence of psychiatric illness, particularly depression and anxiety disorders, and poor quality of life has been observed. Dialysis can also lead to physical symptoms of its own, such as fatigue, loss of appetite, anemia, low blood pressure, and fluid overload, in addition to the symptoms associated with kidney failure. Therefore, this critical review aims to comprehensively understand the impact of dialysis membrane bioincompatibility and the use of varying molecular weight cut-off membranes on the physical and psychological symptoms experienced by dialysis patients. We analyzed the latest research on the correlation between major inflammatory biomarkers released in patients’ blood due to membrane incompatibility, as well as the critical influence of low levels of hemoglobin and vital proteins such as human serum albumin due to the use of high-cut-off membranes and correlated these factors with the physical and psychological symptoms experienced by dialysis patients. Furthermore, our study aims to provide valuable insights into the impact of dialysis on critical symptoms, higher hospitalization rates, and the quality of life of First Nations, as well as child and youth dialysis patients, in addition to diabetic dialysis patients. Our goal is to identify potential interventions aiming to optimize the dialysis membrane and minimize its negative effects on patients, ultimately improving their well-being and long-term outcomes

Investigation on Human Serum Protein Depositions Inside Polyvinylidene Fluoride-Based Dialysis Membrane Layers Using Synchrotron Radiation Micro-Computed Tomography (SR-μCT)

Hemodialysis (HD) membrane fouling with human serum proteins is a highly undesirable process that results in blood activations with further severe consequences for HD patients. Polyvinylidene fluoride (PVDF) membranes possess a great extent of protein adsorption due to hydrophobic interaction between the membrane surface and non-polar regions of proteins. In this study, a PVDF membrane was modified with a zwitterionic (ZW) polymeric structure based on a poly (maleic anhydride-alt-1-decene), 3-(dimethylamino)-1-propylamine derivative and 1,3-propanesultone. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and zeta potential analyses were used to determine the membrane’s characteristics. Membrane fouling with human serum proteins (human serum albumin (HSA), fibrinogen (FB), and transferrin (TRF)) was investigated with synchrotron radiation micro-computed tomography (SR-μCT), which allowed us to trace the protein location layer by layer inside the membrane. Both membranes (PVDF and modified PVDF) were detected to possess the preferred FB adsorption due to the Vroman effect, resulting in an increase in FB content in the adsorbed protein compared to FB content in the protein mixture solution. Moreover, FB was shown to only replace HSA, and no significant role of TRF in the Vroman effect was detected; i.e., TRF content was nearly the same both in the adsorbed protein layer and in the protein mixture solution. Surface modification of the PVDF membrane resulted in increased FB adsorption from both the protein mixture and the FB single solution, which is supposed to be due to the presence of an uncompensated negative charge that is located at the COOH group in the ZW polymer