Search Results (27)

Kidney disease causes the retention of uremic metabolites in blood, which is associated with many comorbidities. Hemodialysis does not properly clear many metabolites, including large, middle-sized, and small protein-bound uremic toxins (PBUTs). Adsorption strategies for metabolite removal require the development of engineered adsorbents with tailored surfaces to increase the binding of desired metabolites. Albumin is uniquely positioned for modifying blood-contacting surfaces to absorb uremic metabolites, as it (i) minimizes non-specific protein adsorption and (ii) binds a range of molecules at Sudlow Sites I and II with different affinities. It is unknown if albumin-modified surfaces retain the adsorption qualities of solution-free albumin, namely, adsorption stability or specificity. Herein, albumin was covalently attached to iron oxide nanoparticles and characterized using multiple methods. Metabolite adsorption was conducted by incubating particles in a model solution of thirty-three uremic metabolites associated with kidney failure. Adsorption efficiency, selectivity, and stability were affected by albumin concentration and incubation time. Metabolite adsorption was found to change with time, and it was more effective on albumin-modified particles than unmodified controls. The findings outlined in this paper are crucial for the design of next-generation advanced blood-contacting materials to enhance dialysis and blood purification for patients with kidney disease. Full article

Kidney failure leads to the accumulation of metabolites in the blood compartment. This build-up of metabolites has been associated with increased mortality and morbidity in these patients; thus, these metabolites are commonly called uremic toxins. The retention of some uremic toxins in the blood results from a strong interaction with serum albumin, preventing their clearance using standard hemodialysis techniques. Adsorbents are considered the next-generation technology for clearing uremic toxins from the blood, and iron oxide magnetic nanoparticles are a promising material due to a high surface area that is easily modified and the ability to remove them from blood with an external magnetic field. Plasma protein adsorption and clot formation kinetics were determined for unmodified and albumin-modified iron oxide magnetic nanoparticles. Albumin was selected because it can bind uremic toxins, and it is commonly used to passivate surfaces. Coatings were formed and characterized using transmission electron microscopy, thermogravimetric analysis, and zeta-potential analysis. Clotting kinetics, total protein assays, and immunoblots were used to analyze the effect surface modification has on protein adsorption events. Unmodified nanoparticles showed rapid clotting and more adsorbed protein compared to albumin-coated iron oxide nanoparticles. Immunoblots show that modified particles showed changes in albumin, protein C, Immunoglobulin G, transferrin, fibrinogen, α1-antitrypsin, vitronectin, plasminogen, prothrombin, and antithrombin levels compared to unmodified controls. The hemocompatibility of adsorbent materials is essential to their clinical application in clearing the blood of uremic toxins. Full article

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis. Full article

The development of materials for uremic toxin removal is under continuous research. In this work, a natural zeolite (clinoptilolite) was modified using tartaric acid through two different methods: conventional reflux heating and ultrasound energy. The resulting materials were used as an adsorbent material for the removal of uremic toxins such as urea, creatinine, and uric acid. In the uremic toxin removal study, it was observed that the material modified using ultrasound for 100 min had the highest removal values (74.49%, 40.31%, and 51.50% for urea, creatinine, and uric acid, respectively), while unmodified zeolite removed 30.57%, 18.07%, and 22.84% of the same toxins. The best results for conventional heating modification were 67.08%, 31.97%, and 32.39%, respectively. Therefore, acid group incorporation considerably improved the adsorption properties of the clinoptilolite. Regarding adsorption kinetics, it was found that the pseudo-second-order model better described the behavior of all the modified materials. Equilibrium adsorption data were adjusted to the Langmuir and Freundlich models. The Freundlich model (multilayer adsorption) described urea adsorption, while the Langmuir model (monolayer adsorption) described creatinine and uric acid. Full article

Serum uremic toxins markedly increase in cats with chronic kidney disease (CKD) and have deleterious consequences. Renaltec is an oral adsorbent that binds uremic toxin precursors in the gut. In this prospective cohort study utilizing 13 purpose-bred cats with remnant kidney model-induced CKD (12 IRIS Stage 2, 1 IRIS Stage 3) eating a standardized renal diet, we aimed to assess the effect of Renaltec administration on serum indoxyl sulfate (IDS) and p-cresol sulfate (pCS) concentrations. Cats were sequentially treated with standard of care for 56 days, 500 mg Renaltec orally once daily for 56 days, and then three months later, 500 mg Renaltec orally twice daily for 56 days. Serum IDS and pCS concentrations were measured 28 and 56 days after the administration of Renaltec. Blood pressure and kidney function were measured before and 56 days after the administration of Renaltec. Significant decreases in serum IDS and pCS concentrations were observed for both once- and twice-daily dosing, particularly during the first 28 days of administration. More cats with BID dosing had clinically significant reductions in serum IDS and pCS concentrations than with SID dosing. Renaltec can reduce the serum concentrations of deleterious gut-derived uremic toxins in cats with CKD. Full article

To reduce the risk of the adsorption of granular activated carbon in the gastrointestinal tract, we successfully produced a hollow-type spherical bacterial cellulose (HSBC) gel containing activated carbon with a particle size of 6 μm. In this study, the aim of which was to develop an effective formulation, we evaluated the stability of activated-carbon-encapsulating HSBC gels under various pH conditions. Activated-carbon-encapsulating HSBC gels (ACEGs) retained the activated carbon without leaking when subjected to agitation in acidic or basic environments. The saturated adsorption amount, calculated using the Langmuir adsorption isotherm, was affected by the target adsorbate and pH conditions. These results indicate that ACEGs can adsorb uremic toxins and their precursors similarly to conventional uremic toxin adsorbents while preventing direct contact between the encapsulated activated carbon and the gastrointestinal tract. Compared to powdered activated carbon, the ACEG is less likely to be adsorbed in the gastrointestinal tract. Therefore, the proposed ACEG is a promising new formulation that will contribute to the treatment of renal failure and improve patients’ compliance with medication. Full article

Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases. Full article

The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). The effect of IS on ferroptosis and the role of IS-related ferroptosis in CKD are not well understood. We used a renal tubular cell model and an adenine-induced CKD mouse model to explore whether IS induces ferroptosis and injury and affects iron metabolism in the renal cells and the kidneys. Our results showed that exposure to IS induced several characteristics for ferroptosis, including iron accumulation, an impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. Exposure to IS triggered intracellular iron accumulation by upregulating transferrin and transferrin receptors, which are involved in cellular iron uptake. We also observed increased levels of the iron storage protein ferritin. The effects of IS-induced ROS generation, lipid peroxidation, ferroptosis, senescence, ER stress, and injury/fibrosis were effectively alleviated by treatments with an iron chelator deferoxamine (DFO) in vitro and the adsorbent charcoal AST-120 (scavenging the IS precursor) in vivo. Our findings suggest that IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys. AST-120 administration may serve as a potential therapeutic strategy. Full article

Chronic kidney disease is the gradual progression of kidney dysfunction and involves numerous co-morbidities, one of the leading causes of mortality. One of the primary complications of kidney dysfunction is the accumulation of toxins in the bloodstream, particularly protein-bound uremic toxins (PBUTs), which have a high affinity for plasma proteins. The buildup of PBUTs in the blood reduces the effectiveness of conventional treatments, such as hemodialysis. Moreover, PBUTs can bind to blood plasma proteins, such as human serum albumin, alter their conformational structure, block binding sites for other valuable endogenous or exogenous substances, and exacerbate the co-existing medical conditions associated with kidney disease. The inadequacy of hemodialysis in clearing PBUTs underscores the significance of researching the binding mechanisms of these toxins with blood proteins, with a critical analysis of the methods used to obtain this information. Here, we gathered the available data on the binding of indoxyl sulfate, p-cresyl sulfate, indole 3-acetic acid, hippuric acid, 3-carboxyl-4-methyl-5-propyl-2-furan propanoic acid, and phenylacetic acid to human serum albumin and reviewed the common techniques used to investigate the thermodynamics and structure of the PBUT–albumin interaction. These findings can be critical in investigating molecules that can displace toxins on HSA and improve their clearance by standard dialysis or designing adsorbents with greater affinity for PBUTs than HSA. Full article

The number of chronic kidney disease (CKD) persons continues to rise in Mexico. They require renal replacement therapy, and in the absence of it, hemodialysis is the major option for their survival. The uremic toxins present in the blood are removed by hemodialysis, which involve membranes. In this study, nonwoven fabrics with modified carbon black nanoparticles in a matrix polymer of Nylon 6 were obtained and evaluated as an adsorbent material of uremic toxins. All nonwoven fabrics were characterized by FTIR, XRD, TGA, SEM, and contact angle measurements and were evaluated as an adsorbent material for the urea toxin and as an albumin retainer. The findings suggest their potential application as a hemodialysis membrane. Nanocomposites had a higher hydrophilic characteristic compared to pure Nylon 6. The average diameter size of the fibers was in the range of 5 to 50 μm. All nanocomposites nonwoven fabrics showed high removal percentages of inulin in a range of 80–85% at 15 min of contact. Most Ny6 Zytel/CB nanocomposites showed a high percentage of urea removal (80 to 90%). Full article

Uremic retention solutes, especially the protein-bound compounds, are toxic metabolites, difficult to eliminate with progressive renal functional decline. They are of particular interest because these uremic solutes are responsible for the pathogenesis of cardiovascular and chronic kidney diseases. Evidence suggests that the relation between uremic toxins, the microbiome, and its host is altered in patients with chronic kidney disease, with the colon’s motility, epithelial integrity, and absorptive properties also playing an important role. Studies found an alteration of the microbiota composition with differences in species proportion, diversity, and function. Since uremic toxins precursors are generated by the microbiota, multiple therapeutic options are currently being explored to address dysbiosis. While an oral adsorbent can decrease the transport of bacterial metabolites from the intestinal lumen to the blood, dietary measures, supplements (prebiotics, probiotics, and synbiotics), and antibiotics aim to target directly the gut microbiota composition. Innovative approaches, such as the modulation of bacterial enzymes, open new perspectives to decrease the plasma level of uremic toxins. Full article

Acute kidney injury (AKI) and gut dysbiosis affect each other bidirectionally. AKI induces microbiota alteration in the gastrointestinal (GI) system, while gut dysbiosis also aggravates AKI. The interplay between AKI and gut dysbiosis is not yet well clarified but worthy of further investigation. The current review focuses on the pathophysiology of this bidirectional interplay and AKI treatment in this base. Both macrophages and neutrophils of the innate immunity and the T helper type 17 cell from the adaptive immunity are the critical players of AKI-induced gut dysbiosis. Conversely, dysbiosis-induced overproduction of gut-derived uremic toxins and insufficient generation of short-chain fatty acids are the main factors deteriorating AKI. Many novel treatments are proposed to deter AKI progression by reforming the GI microbiome and breaking this vicious cycle. Data support the benefits of probiotic treatment in AKI patients, while the results of postbiotics are mainly limited to animals. Prebiotics and synbiotics are primarily discussed in chronic kidney disease patients rather than AKI patients. The effect of adsorbent treatment seems promising, but more studies are required before the treatment can be applied to patients. Immune therapy and some repurposed drugs such as allopurinol are prospects of future treatments and are worth more discussion and survey. Full article

We developed Mixed Matrix Membrane Adsorbers (MMMAs) formed by cellulose acetate and various sorbent particles (activated carbon, zeolites ZSM-5 and clinoptilolite) for the removal of urea, creatinine and uric acid from aqueous solutions, to be used in the regeneration of spent dialysate water from Hemodialysis (HD). This process would allow reducing the disproportionate amount of water consumed and permits the development of closed-loop HD devices, such as wearable artificial kidneys. The strategy of MMMAs is to combine the high permeability of porous membranes with the toxin-capturing ability of embedded particles. The water permeability of the MMMAs ranges between 600 and 1500 L/(h m² bar). The adsorption of urea, the limiting toxin, can be improved of about nine times with respect to the pure cellulose acetate membrane. Flow experiments demonstrate the feasibility of the process in a real HD therapy session. Full article

In this study, temperature-responsive polymer-protein conjugate was synthesized using a “grafting from” concept by introducing a chain transfer agent (CTA) into bovine serum albumin (BSA). The BSA-CTA was used as a starting point for poly(N-isopropylacrylamide) (PNIPAAm) through reversible addition-fragmentation chain transfer polymerization. The research investigations suggest that the thermally responsive behavior of PNIPAAm was controlled by the monomer ratio to CTA, as well as the amount of CTA introduced to BSA. The study further synthesized the human serum albumin (HSA)-PNIPAAm conjugate, taking the advantage that HSA can specifically adsorb indoxyl sulfate (IS) as a uremic toxin. The HSA-PNIPAAm conjugate could capture IS and decreased the concentration by about 40% by thermal precipitation. It was also revealed that the protein activity was not impaired by the conjugation with PNIPAAm. The proposed strategy is promising in not only removal of uremic toxins but also enrichment of biomarkers for early diagnostic applications. Full article

AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection. Full article