Effects of mussel-inspired co-deposition of 2-hydroxymethyl methacrylate and poly (2-methoxyethyl acrylate) on the hydrophilicity and binding tendency of common hemodialysis membranes: Molecular dynamics simulations and molecular docking studies.

Despite advances in the field, hemoincompatibility remains a critical issue for hemodialysis (HD) as interactions between various human blood constituents and the polymeric structure of HD membranes results in complications such as activation of immune system cascades. Adding hydrophilic polymer structures to the membranes is one modification approach that can decrease the extent of protein adsorption. This study conducted molecular dynamics (MD) simulations to understand the interactions between three human serum proteins (fibrinogen [FB], human serum albumin, and transferrin) and common HD membranes in untreated and modified forms. Poly(aryl ether sulfone) (PAES) and cellulose triacetate were used as the common dialyzer polymers, and membrane modifications were performed with 2-hydroxymethyl methacrylate (HEMA) and poly (2-methoxyethyl acrylate) (PMEA), using polydopamine-assisted co-deposition. The MD simulations were used as the framework for binding energy simulations, and molecular docking simulations were also performed to conduct molecular-level investigations between the two modifying polymers (HEMA and PMEA) and FB. Each of the three proteins acted differently with the membranes due to their unique nature and surface chemistry. The simulations show PMEA binds less intensively to FB with a higher number of hydrogen bonds, which reflects PMEA's superior performance compared to HEMA. The simulations suggest PAES membranes could be used in modified forms for blood-contact applications as they reflect the lowest binding energy to blood proteins.

Renewable energy-driven desalination opportunities - A case study.

Renewable energy assisted water desalination technologies are currently becoming attractive as a solution for the water scarcity crisis. Global growth, sustainable development of technologies, and other critical areas are all significantly impacted by water access. Higher living standards and population growth along with industrial developments have resulted in an increased rate of water consumption. Furthermore, more countries are experiencing severe droughts while their drinkable water resources are being limited. Iran, as our case study is one of the countries suffering from such a problem as it has entered into water-bankruptcy period. This study analyzed the country's general water background and its renewable energy status, in addition to the potential in renewable energy assisted desalination (RED). Research reported suggests that Iran's potential in RED water production is more than 28 billion cubic meter in the case limited to only wind and solar potentials put into practice. Thus, Iran should be considered as a prototype in the solutions for water scarcity in cases of proper investment and planning. The critical case study offers an in-depth analysis which could be used as a strategic guide for different regions as it offers more secure solutions to future water concerns.

Recent advances in thin film composites membranes for brackish groundwater treatment with critical focus on Saskatchewan water sources.

Drinking water scarcity is an ever-increasing global concern. This issue appears as a greater threat to the countries with no access to sea water resources or rivers, since their potential water resources are only limited to ground waters only. There are serious concerns with the treatment of ground water resources, including landfill leachates, agricultural contaminations (pesticides, herbicides, and fertilizers), and rural contaminations. Membrane separation has been proved to be the governing technology in water and wastewater treatment plants, as these methods are responsible for more than half of the market share of the world's desalination capacity. This study intends to offer a holistic view of the groundwater contamination with specific focus on Saskatchewan province in Canada, and the recent efforts in the groundwater treatment using thin film composite membrane technology. This study begins with an introduction of the general aspects of ground water and membrane separation, polluting agents, and their sources. It is followed by a discussion of Saskatchewan's groundwater status and various issues. Furthermore, the recent research that became available since 2010 is reviewed in details and the results are summarized with respect to purification efficiency. Different affecting parameters in a groundwater-thin film composite system are synthesized and an in-depth overview is presented.

Review of post-combustion carbon dioxide capture technologies using activated carbon.

Carbon dioxide (CO2) is the largest anthropogenic greenhouse gas (GHG) on the planet contributing to the global warming. Currently, there are three capture technologies of trapping CO2 from the flue gas and they are pre-combustion, post-combustion and oxy-fuel combustion. Among these, the post-combustion is widely popular as it can be retrofitted for a short to medium term without encountering any significant technology risks or changes. Activated carbon is widely used as a universal separation medium with series of advantages compared to the first generation capture processes based on amine-based scrubbing which are inherently energy intensive. The goal of this review is to elucidate the three CO2 capture technologies with a focus on the use of activated carbon (AC) as an adsorbent for post-combustion anthropogenic CO2 flue gas capture prior to emission to atmosphere. Furthermore, this coherent review summarizes the recent ongoing research on the preparation of activated carbon from various sources to provide a profound understanding on the current progress to highlight the challenges of the CO2 mitigation efforts along with the mathematical modeling of CO2 capture. AC is widely seen as a universal adsorbent due to its unique properties such as high surface area and porous texture. Other applications of AC in the removal of contaminants from flue gas, heavy metal and organic compounds, as a catalyst and catalyst support and in the electronics and electroplating industry are also discussed in this study.

The influence of aggregation of latex particles on membrane fouling attachments & ultrafiltration performance in ultrafiltration of latex contaminated water and wastewater.

The goal of the present study was to investigate the influence of latex particle aggregation on membrane fouling attachments and the ultrafiltration performance of simulated latex effluent using Cetyltrimethyl Ammonium Bromide (CTAB) as a cationic surfactant. Hydrophilic polysulfone and ultrafilic flat heterogeneous membranes, with molecular weight cut off (MWCO) of 60,000 and 100,000, respectively, as well as hydrophobic polyvinylidene difluoride with MWCO of 100,000, were used under a constant flow rate and cross-flow mode in ultrafiltration of latex solution. In addition, a polycarbonate flat membrane with uniform pore size of 0.05µm was likewise used during the experiment. The effects of CTAB on the latex particle size distribution were investigated at various concentrations, different treatment times, and diverse agitation duration times. The effects of CTAB on the zeta potential of membrane surfaces and latex particles were also investigated. The data obtained indicate that the particle size distribution of treated latex effluent experienced significant shifts in the peaks toward a larger size range caused by the aggregation of particles. As a result, the mass of fouling contributing to pore blocking and the irreversible fouling were noticeably reduced. The optimum results occurred in the instance when CTAB was added at the critical micelle concentration of 0.36g/L, for the duration of 10min and with minimal agitation. Notably, a higher stirring rate had an overall negative effect on the membrane fouling minimization.

Corrigendum to "WCN24-658 Comparative Analysis of Zwitterionic Materials and Polyvinyl Pyrrolidone for Enhancing Dialysis Membrane Hemocompatibility and Psychological Symptoms in Patients" [Kidney International Reports Volume 9, Issue 4, Supplement, April 2024, Pages S362-S363].

[This corrects the article DOI: 10.1016/j.ekir.2024.02.757.].

Corrigendum to "WCN24-660 Comparative Analysis of High Flux and Low Flux Dialysis Membranes: In-Situ Synchrotron Imaging and Experimental Ex-Vivo Studies" [Kidney International Reports Volume 9, Issue 4, Supplement, April 2024, Page S363].

[This corrects the article DOI: 10.1016/j.ekir.2024.02.758.].

Aminolysis-Based Zwitterionic Immobilization on Polyethersulfone Membranes for Enhanced Hemocompatibility: Experimental, Computational, and Ex Vivo Investigations.

Dialysis membranes are not hemocompatible with human blood, as the patients are suffering from the blood-membrane interactions' side effects. Zwitterionic structures have shown improved hemocompatibility; however, their complicated synthesis hinders their commercialization. The goal of the study is to achieve fast functionalization for carboxybetaine and sulfobetaine zwitterionic immobilization on PES membranes while comparing the stability and the targeted hemocompatibility. The chemical modification approach is based on an aminolysis reaction. Characterization, computational simulations, and clinical analysis were conducted to study the modified membranes. Atomic force microscopy (AFM) patterns showed a lower mean roughness for carboxybetaine-modified (6.3 nm) and sulfobetaine-modified (7.7 nm) membranes compared to the neat membrane (52.61 nm). The pore size of the membranes was reduced from values above 50 nm for the neat PES to values between 2 and 50 nm for zwitterionized membranes, using Brunauer-Emmett-Teller (BET) analysis. More hydrophilic surfaces led to a growth equilibrium water content (EWC) of nearly 6% for carboxybetaine and 10% for sulfobetaine-modified membranes. Differential scanning calorimetry (DSC) measurements were 12% and 16% stable water for carboxybetaine- and sulfobetaine-modified membranes, respectively. Sulfobetaine membranes showed better compatibility with blood with respect to C5a, IL-1a, and IL-6 biomarkers. Aminolysis-based zwitterionization was found to be suitable for the improvement of hemodialysis membranes. The approach introduced in this paper could be used to modify the current dialysis membranes with minimal change in the production facilities.

A comprehensive exploration of chronic kidney disease and dialysis in Canada's Indigenous population: from epidemiology to genetic influences.

PURPOSE: This study aims to review the escalating prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) among Canada's Indigenous population, focusing on risk factors, hospitalization and mortality rates, and disparities in kidney transplantation. The study explores how these factors contribute to the health outcomes of this population and examines the influence of genetic variations on CKD progression. METHODS: The review synthesizes data on prevalence rates, hospitalization and mortality statistics, and transplantation disparities among Indigenous individuals. It also delves into the complexities of healthcare access, including geographical, socioeconomic, and psychological barriers. Additionally, the manuscript investigates the impact of racial factors on blood characteristics relevant to dialysis treatment and the genetic predispositions influencing disease progression in Indigenous populations. RESULTS: Indigenous individuals exhibit a higher prevalence of CKD and ESRD risk factors such as diabetes and obesity, particularly in regions like Saskatchewan. These patients face a 77% higher risk of death compared to their non-Indigenous counterparts and are less likely to receive kidney transplants. Genetic analyses reveal significant associations between CKD and specific genomic variations. Through analyses, we found that healthy Indigenous individuals may have higher levels of circulating inflammatory markers, which could become further elevated for those with CKD. In particular, they may have higher levels of C-reactive protein (CRP) fibrinogen, as well as genomic variations that affect IL-6 production and the function of von Willebrand Factor (vWF) which has critical potential influence on the compatibility with dialysis membranes contributing to complications in dialysis. CONCLUSION: Indigenous people in Canada are disproportionately burdened by CKD and ESRD due to socioeconomic factors and potential genetic predispositions. While significant efforts have been made to assess the socioeconomic conditions of the Indigenous population, the genetic factors and their potential critical influence on compatibility with dialysis membranes, contributing to treatment complications, remain understudied. Further investigation into these genetic predispositions is essential.

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.

Heparin-Immobilized Polyethersulfone for Hemocompatibility Enhancement of Dialysis Membrane: In Situ Synchrotron Imaging, Experimental, and Ex Vivo Studies.

The goal of the current study is to enhance the hemocompatibility of polyethersulfone (PES) membranes using heparin immobilization. Heparin was immobilized covalently and via electrostatic interaction with the positively charged PES surface (pseudo-zwitterionic (pZW) complex) to investigate the influence of each method on the membrane hemocompatibility. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging, available at the Canadian Light Source (CLS), was used to critically assess the fibrinogen adsorption to the newly synthesized membranes qualitatively and quantitatively using an innovative synchrotron-based X-ray tomography technique. The surface roughness of the synthesized membranes was tested using atomic force microscopy (AFM) analysis. The membrane hemocompatibility was examined through the ex vivo clinical interaction of the membranes with patients' blood to investigate the released inflammatory biomarkers (C5a, IL-1α, IL-1ß, IL-6, vWF, and C5b-9). The presence and quantitative analysis of a stable hydration layer were assessed with DSC analysis. Surface modification resulted in reduced surface roughness of the heparin-PES membrane. Both types of heparin immobilization on the PES membrane surface resulted in a decrease in the absolute membrane surface charge from -60 mV (unmodified PES) to -13 mV for the pZW complex and -9.16 mV for the covalently attached heparin, respectively. The loss of human serum fibrinogen (FB) was investigated using UV analysis. The PES membrane modified with the heparin pseudo-ZW complex showed increased FB retention (90.5%), while the unmodified PES membrane and the heparin covalently attached PES membrane exhibited approximately the same level of FB retention (81.3% and 79.8%, respectively). A DSC analysis revealed an improvement in the content of the hydration layer (32% of non-freezable water) for the heparin-coated membranes compared to the unmodified PES membrane (2.84%). An SR-µCT analysis showed that the method of heparin immobilization significantly affects FB adsorption distribution across the membrane thickness. A quantitative analysis using SR-µCT showed that when heparin is attached covalently, FB tends to be deposited inside the membrane pores at the top (layer index 0-40) membrane regions, although its content peak distribution shifted to the membrane surface, whereas the unmodified PES membrane holds 90% of FB in the middle (layer index 40-60) of the membrane. The ex vivo hemocompatibility study indicates an improvement in reducing the von Willebrand factor (vWF) for the heparin pseudo-ZW PES membrane compared to the covalently attached heparin and the untreated PES.

In-situ synchrotron quantitative analysis of competitive adsorption tendency of human serum proteins on polyether sulfone clinical hemodialysis membrane.

Comprehensive understanding of protein adsorption phenomenon on membrane surface during hemodialysis (HD) is one of the key moments for development of hemocompatible HD membrane. Though many mechanisms and kinetics of protein adsorption on some surface have been studied, we are still far away from complete understanding and control of this process, which results in a series of biochemical reactions that causes severe complications with health and even the death among HD patients. The aim of this study is to conduct quantitative analysis of competitive adsorption tendency of human serum protein on polyether sulfone (PES) clinical dialysis membrane. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging available at the Canadian Light Source (CLS) was conducted to assess human serum proteinbinding and undertake the corresponding quantitative analysis.The competitive adsorption of Human protein albumin (HSA), fibrinogen (FB) and transferrin (TRF) were tested from single and multiple protein solution. Furthermore, in-vitro human serum protein adsorption on clinical dialyzers was investigated using UV-Visible to confirm the competitive adsorption tendency. Results showed that when proteins were adsorbed from their mixture, FB content (among proteins) in the adsorbed layer increased from 3.6% mass (content in the initial solution) to 18% mass and 12%, in case of in situ quantitative and invitro analysis, respectively. The increase in FB content was accompanied by the decrease in the HSA content, while TRF remained on approximately on the same level for both cases. Overall, the percentage of HSA adsorption ratio onto the HD membrane has dropped approximately 10 times when HSA was adsorbed in competition with other proteins, compared to the adsorption from single HSA solution. The substitution of HSA with FB was especially noticeable when HSA adsorption from its single solution was compared with the case of the protein mixture. Moreover, SR-µCT has revealed that FB when adsorbed from a protein mixture solution is located predominately in the middle of the membrane, whereas the peak of the distribution is shifted to membrane bottom layers when adsorption from FB single solution takes place. Results showed that HSA FB and TRF adsorption behavior observations are similar on both in-situ small scale and clinical dialyzer of the PES membrane.

In-situ synchrotron imaging, experimental, and computational investigations on the efficiency of Trametes versicolor laccase on detoxification of P-Cresyl Sulfate (PCS) Protein Bound Uremic Toxin (PBUT).

Protein bound uremic toxins (PBUTs) are small substances binding to larger proteins, mostly human serum albumin (HSA), and are challenging to remove by hemodialysis (HD). Among different classes of PBUTs, p-cresyl sulfate (PCS) is the most widely used marker molecule and major toxin, as 95 % is bound to HSA. PCS has a pro-inflammatory effect and increases both the uremia symptom score and multiple pathophysiological activities. High-flux HD to clear PCS leads to serious loss of HSA, which results in a high mortality rate. The goal of the present study is to investigate the efficacy of PCS detoxification in serum of HD patients using a biocompatible laccase enzyme from Trametes versicolor. Molecular docking was used to gain an in-depth understanding of the interactions between PCS and the laccase to identify the functional group(s) responsible for ligand-protein receptor interactions. UV-Vis spectroscopy and gas chromatography-mass spectrometry (GC-MS) were used to assess the detoxification of PCS. GC-MS was used to identify the detoxification byproducts and their toxicity was assessed using docking commutations. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging available at the Canadian Light Source (CLS) was conducted to assess HSA binding with PCS before and after detoxification with laccase and undertake the corresponding quantitative analysis. GC-MS analyses confirmed the detoxification of PCS with laccase at a concentration of 500 mg/L. The potential pathway of PCS detoxification in the presence of the laccase was identified. Increasing laccase concentration led to the formation of m-cresol, as indicated by the corresponding absorption in the UV-Vis spectra and a sharp peak on the GC-MS spectra. Our analysis provides insight into the general features of PCS binding on Sudlow site II, as well as insights into PCS detoxification product interactions. The average affinity energy for detoxification products was lower than that of PCS. Even though some byproducts showed potential toxicity, the level was lower than for PCS based on toxicity indexes (e.g., LD50/LC50, carcinogenicity, neurotoxicity, mutagenicity). In addition, these small compounds can also be more easily removed by HD compared to PCS. SR-µCT quantitative analysis showed adhesion of the HSA to a significant reduced extent in the presence of the laccase enzyme in bottom sections of the polyarylethersulfone (PAES) clinical HD membrane tested. Overall, this study opens new frontiers for PCS detoxification.

Impact of Membrane Modification and Surface Immobilization Techniques on the Hemocompatibility of Hemodialysis Membranes: A Critical Review.

Despite significant research efforts, hemodialysis patients have poor survival rates and low quality of life. Ultrafiltration (UF) membranes are the core of hemodialysis treatment, acting as a barrier for metabolic waste removal and supplying vital nutrients. So, developing a durable and suitable membrane that may be employed for therapeutic purposes is crucial. Surface modificationis a useful solution to boostmembrane characteristics like roughness, charge neutrality, wettability, hemocompatibility, and functionality, which are important in dialysis efficiency. The modification techniques can be classified as follows: (i) physical modification techniques (thermal treatment, polishing and grinding, blending, and coating), (ii) chemical modification (chemical methods, ozone treatment, ultraviolet-induced grafting, plasma treatment, high energy radiation, and enzymatic treatment); and (iii) combination methods (physicochemical). Despite the fact that each strategy has its own set of benefits and drawbacks, all of these methods yielded noteworthy outcomes, even if quantifying the enhanced performance is difficult. A hemodialysis membrane with outstanding hydrophilicity and hemocompatibility can be achieved by employing the right surface modification and immobilization technique. Modified membranes pave the way for more advancement in hemodialysis membrane hemocompatibility. Therefore, this critical review focused on the impact of the modification method used on the hemocompatibility of dialysis membranes while covering some possible modifications and basic research beyond clinical applications.

Influence of zwitterionic structure design on mixed matrix membrane stability, hydrophilicity, and fouling resistance: A computational study.

Zwitterion-based mixed matrix membranes (MMMs) with designed characteristics of enhanced water flux, selectivity, and fouling mitigation have emerged as a new class of advanced membranes for oilsands process-affected wastewater (OSPW) treatment. Zwitterions (ZW) characterized by super-hydrophilicity and excellent fouling resistance have gained increasing attention in membrane modification research. In general, zwitterion properties are determined by the chemistry and structural properties of its constituents, including the polymer backbone, charged moieties, spacers, as well as molecular configuration. This study used molecular dynamics simulation (MDS) to investigate the effects of polymer backbone (PB), spacer length (SL), and spacer chemistry (SC) on ZW-based MMM properties such as stability, hydrophilicity, and oil-antifouling potentiality. Membrane performance was also assessed at high temperatures (50, 70, and 90 °C. The results suggest PB, SL, and SC all influence the resultant MMM performance, with SL being the most impactful structural parameter on stability and hydrophilicity. Variation of SL was suspected to alter the ionic association and partial charges of zwitterionic moieties, which affect their ability to interact with the polymer network and water molecules. Spacer chemistry (i.e., hydroxyl (-OH) groups) can initiate self-association between zwitterionic charged groups having short SL, lessening their inter-molecular networking ability. However, for ZWs with long SL, the presence of hydroxyl groups on the spacer can result in the formation of hydrogen bonds and/or electrostatic interactions with other ZW molecules and polyvinylidene difluoride (PVDF) polymer chains or water molecules, improving membrane stability and hydrophilicity. High temperatures reduced membrane stability but to a lesser extent for MMMs compared to unmodified PVDF membrane. While temperature greatly influenced membrane hydrophilicity, the impacts were membrane-specific. The oil-fouling propensity of pristine PVDF membrane increased with temperature but of MMMs appeared stable across the temperature range studied.

Influence of UV-irradiation intensity and exposure duration on the hemobiocompatibility enhancement of a novel synthesized phosphobetaine zwitterions polyethersulfone clinical hemodialysis membranes.

To improve the biocompatibility of polyethersulfone (PES) membranes utilized for biomedical hemodialysis (HD) applications, surface grafting with hydrophilic polymers has become a reliable modification strategy. Like most photochemical catalyzed reactions, UV-assisted grafting is distinctly advantageous for inducing permanent surface chemistry, enhancing hydrophilicity, improving morphology, and surface charge of membranes. PES membranes may be hydrophilic and chemically stable; however, they also have low protein-binding capacity and very susceptible to fouling and target analyte binding. In this study, novel zwitterionic polymers (PVP-ZW) have been synthesized by UV-assisted grafting PVP to a phosphobetaine monomer in a reaction involving dimethylamino and dioxaphospholane-2-oxide terminal groups in an NVP monomer solution at varying UV exposure conditions. The highlight of the present study is the investigation of the hemocompatibility of coated PES HD membranes at varying UV exposure conditions with respect to membrane chemistry and morphology and its influence on human serum protein adsorption. A clinical investigation of inflammatory biomarker release from incubated coated membranes within uremic blood samples of HD patients reveals they are weak complement and coagulation activators compared to bare PES membrane. The trend of fibrinogen adsorption on coated PES membranes was observed to increase with reducing UV intensity and exposure duration. Fibrinogen adhesion only increased with roughened membrane surfaces, and this also led to the formation of biological activation pathways hindering biocompatibility. Resistance against fibrinogen absorption on zwitterionic modified PES membrane could be linked with the creation of electrostatically induced neutral zwitterionic PVP-phosphobetaine hydration layer with hydrophilic character. Experimental results are accompanied by spectroscopic and morphological imaging evidence. Zwitterion coated PES membranes (PES-PVP-ZW) fabricated from higher UV intensities through longer exposure durations showed significant presence of surface deformations in the forms of inherent exfoliations due to harsh UV reaction conditions. The zeta potential and surface roughness of coated membranes also played significant role in the fibrinogen adsorption on PES membranes during ultrafiltration.

Advancing Discovery Research in Nephrology in Canada: A Conference Report From the 2021 Molecules and Mechanisms Mediating Kidney Health and Disease (M3K) Scientific Meeting and Investigator Summit.

Purpose of conference: New discoveries arising from investigations into fundamental aspects of kidney development and function in health and disease are critical to advancing kidney care. Scientific meetings focused specifically on fundamental biology of the kidney can facilitate interactions, support the development of collaborative groups, and accelerate translation of key findings. The Canadian fundamental kidney researcher community has lacked such a forum. On December 3 to 4, 2021, the first Molecules and Mechanisms Mediating Kidney Health and Disease (M3K) Scientific Meeting and Investigator Summit was held to address this gap with the goal of advancing fundamental kidney research nationally. The meeting was held virtually and was supported by a planning and dissemination grant from the Canadian Institutes of Health Research. Attendees included PhD scientists, nephrology clinician scientists, engineers, industry representatives, graduate students, medical residents, and fellows. Sources of information: This report was prepared from the scientific program, registration numbers, and details obtained from the online platform WHOVA, and summaries written by organizers and participants of the 2021 meeting. Methods: A 21-person team, consisting of the organizing committee members and participants from the meeting, was assembled. Key highlights of the meeting and future directions were identified and the team jointly assembled this report. Key findings: Participation in the meeting was strong, with more than 140 attendees across a range of disciplines. The program featured state-of-the-art presentations on diabetic nephropathy, the immune system, kidney development, and fibrosis, and was heavily focused on trainee presentations. The moderated "Investigator Summit" identified key barriers to research advancement and discussed strategies for overcoming them. These included establishment of a pan-Canadian fundamental kidney research network, development of key resources, cross-pollination with clinical nephrology, better reintegration into the Canadian Society of Nephrology, and further establishment of identity and knowledge translation. Limitations and implications: The 2021 M3K meeting represented a key first step in uniting fundamental kidney researchers in Canada. However, it was universally agreed that regular meetings were necessary to sustain this momentum. The proceedings of this meeting and future actions to sustain the M3K Scientific Meeting and Investigator Summit are presented in this article.

Objectif de la conférence: De nouvelles découvertes découlant des enquêtes sur les aspects fondamentaux du développement et de la fonction des reins en santé ou malades sont essentielles pour faire progresser les soins rénaux. Les réunions scientifiques axées spécifiquement sur la biologie fondamentale du rein peuvent faciliter les interactions, appuyer le développement de groupes de collaboration et accélérer l'application des principaux résultats. La communauté canadienne des chercheurs fondamentaux en néphrologie a manqué d'un tel forum. Les 3 et 4 décembre 2021, le premier Sommet des chercheurs et la réunion scientifique M3K (Molecules and Mechanisms Mediating Kidney Health and Disease) sur les molécules et les médiateurs de la santé et des maladies rénales ont eu lieu pour combler cette lacune; l'objectif était de faire progresser la recherche fondamentale en néphrologie à l'échelle nationale. La réunion s'est tenue virtuellement et était financée par une subvention de planification et de diffusion des Instituts de recherche en santé du Canada. Des doctorants, cliniciens-chercheurs en néphrologie, ingénieurs, représentants de l'industrie, étudiants diplômés, résidents en médecine et en surspécialisation figuraient parmi les participants. Sources: Ce rapport a été préparé à partir du program scientifique, des informations et des numéros d'inscription tirés de la plateforme en ligne WHOVA, et des résumés rédigés par les organisateurs et les participants à la réunion de 2021. Méthodologie: Une équipe de 20 personnes composée de membres du comité organisateur et de participants à la réunion a été formée. Les principaux points saillants de la réunion et les orientations futures ont été déterminés, puis l'équipe a rédigé conjointement le présent rapport. Principaux résultats: La réunion s'est avérée un succès; plus de 140 personnes provenant d'un large éventail de disciplines y ont participé. Le program comprenait des présentations de pointe sur la néphropathie diabétique, le système immunitaire, le développement des reins et la fibrose, et était fortement axé sur des présentations par des stagiaires. Le « Sommet des chercheurs ¼, animé par un modérateur, a permis de déterminer les principaux obstacles à l'avancement de la recherche et de discuter des stratégies pour les surmonter. Ces dernières incluent notamment la création d'un réseau pancanadien de recherche fondamentale en néphrologie, le développement de ressources clés, la pollinisation croisée avec la néphrologie clinique, une « meilleure réintégration dans la Société canadienne de néphrologie ¼ et la poursuite de l'établissement de l'identité et de l'application des connaissances. Limites et implications: La réunion M3K de 2021 a constitué une première étape clé dans l'unification des chercheurs fondamentaux en néphrologie au Canada. On a cependant universellement convenu que des réunions régulières étaient nécessaires pour maintenir cet élan. Le compte rendu de cette réunion ainsi que les actions futures pour soutenir la réunion scientifique M3K et le Sommet des chercheurs sont présentés dans le présent article.

Molecular dynamics simulation for membrane separation and porous materials: A current state of art review.

Computational frameworks have been under specific attention within the last two decades. Molecular Dynamics (MD) simulations, identical to the other computational approaches, try to address the unknown question, lighten the dark areas of unanswered questions, to achieve probable explanations and solutions. Owing to their complex microporous structure on one side and the intricate biochemical nature of various materials used in the structure, separative membrane materials possess peculiar degrees of complications. More notably, as nanocomposite materials are often integrated into separative membranes, thin-film nanocomposites and porous separative nanocomposite materials could possess an additional level of complexity with regard to the nanoscale interactions brought to the structure. This critical review intends to cover the recent methods used to assess membranes and membrane materials. Incorporation of MD in membrane technology-related fields such as desalination, fuel cell-based energy production, blood purification through hemodialysis, etc., were briefly covered. Accordingly, this review could be used to understand the current extent of MD applications for separative membranes. The review could also be used as a guideline to use the proper MD implementation within the related fields.

Hemodialysis biocompatibility mathematical models to predict the inflammatory biomarkers released in dialysis patients based on hemodialysis membrane characteristics and clinical practices.

Chronic kidney disease affects millions of people around the globe and many patients rely on hemodialysis (HD) to survive. HD is associated with undesired life-threatening side effects that are linked to membrane biocompatibility and clinical operating conditions. The present study develops a mathematical model to predict the inflammatory biomarkers released in HD patients based on membrane morphology, chemistry, and interaction affinity. Based on the morphological characteristics of two clinical-grade HD membrane modules (CTA and PAES-PVP) commonly used in Canadian hospitals, a molecular docking study, and the release of inflammatory cytokines during HD and in vitro incubation experiments, we develop five sets of equations that describe the concentration of eight biomarkers (serpin/antithrombin-III, properdin, C5a, 1L-1α, 1L-1ß, C5b-9, IL6, vWF). The equations developed are functions of membrane properties (pore size, roughness, chemical composition, affinity to fibrinogen, and surface charge) and HD operating conditions (blood flow rate, Qb, and treatment time, t). We expand our model based on available clinical data and increase its range of applicability in terms of flow rate and treatment time. We also modify the original equations to expand their range of applicability in terms of membrane materials, allowing the prediction and validation of the inflammatory response of several clinical and synthesized membrane materials. Our affinity-based model solely relies on theoretical values of molecular docking, which can significantly reduce the experimental load related to the development of more biocompatible materials. Our model predictions agree with experimental clinical data and can guide the development of novel materials and support evidence-based membrane synthesis of HD membranes, reducing the need for trial-and-error approaches.

Protein-bound uremic toxins (PBUTs) in chronic kidney disease (CKD) patients: Production pathway, challenges and recent advances in renal PBUTs clearance.

Uremic toxins, a group of uremic retention solutes with high concentration which their accumulation on the body makes several biological problems, have recently gained a large interest. The importance of this issue more targets patients with compromised kidney function since the presence of these toxins in their bodies contributes to serious illness and death. It is reported that around 14% of people are subjected of CKD's problems. Among different classifications of uremic toxins, protein bound uremic toxins are poorly removed from the body as they tightly bind to proteins like serum albumin. A deeper and closer understanding of methods for removing protein bound uremic toxins and their efficiency is of paramount importance. This article discussed the most critical protein bound uremic toxins from different points of view including their chemistry, binding sites, interactions, and their biological impacts. Concerning the toxicity and high concentration, p-cresyl sulfate (PCS), Indoxyl sulfate (IS), 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), and Indole- 3-acetic acid (IAA) was chosen to study in this article. Results offered that the functional groups of mentioned PBUTs and the way that they interact with the adsorbent play an important role in finding substances for removal of them. Furthermore, the development of nanoparticle (NPs) for promising biomedical purposes has been explored. However, there is still a need for further investigation to find biocompatible substances focusing on the removal of PBUTs. PBUTs are a unique class of uremic toxins whose renal clearance mechanisms and role in uremic pathophysiology are still unclear. This review outlines the biochemical aspects of PBUT/protein binding in a view to explaining their renal formation to elimination mechanisms; some examples are drawn from routes involving albumin-binding with indoxyl sulphate, p-cresyl sulfate, p-cresyl glucuronide and hippuric acid. We have also highlighted the kinetic behaviors during dialytic removal of PBUTs to address future concerns regarding dialytic therapy.