Search Results (19)

Protein-bound uraemic toxins (PBUTs), such as indoxyl sulphate (IS) and p-cresyl sulphate (PCS), are poorly cleared by conventional haemodialysis (HD) or haemodiafiltration (HDF). Haemoadsorption combined with HD (HAHD) using the novel pHA130 cartridge may increase PBUT removal, and this trial aimed to compare its efficacy and safety with HDF in patients with end-stage renal disease (ESRD). In this single-centre, open-label trial, 30 maintenance HD patients were randomized (1:1:1) to HDF once every two weeks (HDF-q2w), HAHD once every two weeks (HAHD-q2w), or HAHD once weekly (HAHD-q1w) for 8 weeks, with the primary endpoint being the single-session reduction ratio (RR) of IS. The combined HAHD group (n = 20) demonstrated a significantly greater IS reduction than the HDF-q2w group (n = 10) (46.9% vs. 31.8%; p = 0.044) and superior PCS clearance (44.6% vs. 31.4%; p = 0.003). Both HAHD regimens significantly reduced predialysis IS levels at Week 8. Compared with HDF, weekly HAHD provided greater relief from pruritus and improved sleep quality, with comparable adverse events among groups. In conclusion, HAHD with the pHA130 cartridge is more effective than HDF for enhancing single-session PBUT removal and alleviating uraemic symptoms in patients with ESRD, with weekly application showing optimal symptomatic benefits. Full article

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions. Full article

Background: Removal of large uraemic toxins is still a challenge. Haemodiafiltration (HDF) has produced some results, although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium cut-off, high-retention-onset membranes have been recently developed, introducing the concept therapy called expanded haemodialysis (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress. Methods: A prospective longitudinal multicentre study was conducted for 3 months among 24 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high-flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Results: Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane, without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we did not find differences in removal ratio and Kt/V. Reduction in the erythropoietin resistance index was observed in patients treated with ViE-X membrane due to their lower dialysis vintage. Conclusions: The higher albumin loss during HDx has no effects on pre-dialysis serum albumin. HDx with Theranova in the presence of lower session length, lower Qb, lower convective dose, and lower instantaneous clearance reached the same dialysis efficacy compared to HDF. Full article

Chronic kidney disease is a global health burden with a rising incidence and prevalence in developed and developing nations. Once established, it results in a progressive accumulation of a myriad of uraemic toxins. Peritoneal dialysis (PD) uses the body’s peritoneal membrane to remove these toxins across a semipermeable membrane to restore and maintain homeostasis. Traditionally, dialysis adequacy has been measured through clearance of urea and creatinine. However, numerous studies have shown marginal links comparing the clearance of urea and creatinine with clinical outcomes reflected in the recent changes to the ISPD guidelines on dialysis adequacy. Instead, attention has focused on protein-bound uraemic toxins (PBTs). Produced by gut bacteria, these molecules are highly protein-bound and poorly removed by either dialysis or absorptive agents. Elevated concentrations of molecules such as p-cresyl sulfate and indoxyl sulfate have been associated with abnormal cellular function and poor patient outcomes. However, widespread use of these measures to determine dialysis adequacy has been limited by the need for specialized techniques required for measurement. Altering the gut microbiome to reduce generation of PBTs through increased dietary fiber might be an alternate approach to better patient outcomes, with some initial positive reports. This report explores advantages and limitations of measuring uraemic toxins in PD, now and in the foreseeable future. Full article

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis. Full article

Infections with Shiga toxin-producing Escherichia coli (STEC) are increasing in Denmark and elsewhere. STEC is also the most frequent cause of haemolytic uraemic syndrome (HUS) in Danish children. Most cases are considered sporadic, while approximately one-third can be attributed to a known source of infection. Hence, we examined sources of sporadic STEC infection in Denmark. From January 2018 to December 2020, we conducted a prospective nationwide case–control study among Danish adults and children. Cases with confirmed positive STEC infection were notified infections within the national laboratory surveillance system. Control persons were randomly selected from the Danish Civil Registration System, individually matched in age in 5-year bands and sex. Participants were invited by an electronic letter to complete either an adult or child questionnaire online. Univariate and adjusted matched odds ratios were computed for adults and children using conditional logistic regression. The study recruited 1583 STEC cases and 6228 controls. A total of 658 cases (42%) and 2155 controls (35%) were included in the analysis. Depending on age, univariate analysis adjusted for socio-demographic determinants showed that the consumption of boiled beef (mOR = 2.2, 95% confidence interval (CI): 1.6–3.1) and fried minced beef (mOR = 1.6, CI: 1.2–2.1), drinking raw (unpasteurized) milk (mOR = 11, CI 1.1–110), eating grilled food (mOR = 9.8, CI: 5.6–17) and having a household member using diapers (mOR = 2.1, CI: 1.4–3.2) were determinants of sporadic STEC infection. Further multivariate adjusted analysis resulted in the same determinants. This study confirms that beef is an overall important risk factor for STEC infection in Denmark. We also present evidence that a proportion of sporadic STEC infections in Denmark are determined by age-specific eating habits, environmental exposures and household structure, rather than being exclusively food-related. These findings are relevant for targeted public health actions and guidelines. Full article

Recent studies place great importance on Protein-Bound Uraemic Toxins (PBUT) in the context of etiopathogenesis of chronic kidney disease-associated pruritus (CKD-aP). This study aimed to investigate the possible contribution of free and total Indoxyl Sulfate (IS) and p-Cresol Sulfate (PCS) to the cause of CKD-aP. Group A included 64 patients on maintenance haemodialysis (HD) with CKD-aP. Group B included 62 patients on maintenance HD that did not report CKD-aP, and group C included 50 healthy controls. Pruritus severity was assessed using a Numerical Rating Scale (NRS). Moreover, other tools like UP-Dial, ItchyQoL, and the 4-Item Itch Questionnaire evaluating CKD-aP were completed by the patients. The serum levels of free and total IS and PCS concentrations were measured using the Ultra Performance Liquid Chromatography System. No significant difference in the serum level of free and total IS, or PCS, was observed between the patients who reported CKD-aP and those without pruritus. Moreover, there was no correlation between serum IS or PCS levels and the severity of the itch. Our study does not support earlier findings about higher levels of IS and PCS in patients reporting CKD-aP. Further studies will be needed to investigate these discrepancies as well as to understand the cause of CKD-aP. Full article

Kidney transplant candidates and kidney transplant recipients (KTRs) are at particular risk of severe complications of COVID-19 disease. In Western countries, mortality in affected hospitalized KTRs ranges between 19% and 50%. COVID-19 vaccination remains the most important measure to prevent the severity of infection in candidates and recipients of kidney transplant. However, the uraemic condition may affect the vaccine-induced immunity in patients with advanced chronic kidney disease (CKD) and in KTRs. Retention of uraemic toxins, dysbiosis, dysmetabolism, and dialysis can diminish the normal response to vaccination, leading to dysfunction of inflammatory and immune cells. In KTRs the efficacy of vaccines may be reduced by the immunosuppressive medications, and more than half of kidney transplant recipients are unable to build an immune response even after four administrations of anti-COVID-19 vaccines. The lack of antibody response leaves these patients at high risk for SARS-CoV-2 infection and severe COVID-19 disease. The aim of the present review is to focus on the main reasons for the impaired immunological response among candidates and kidney transplant recipients and to highlight some of the present options available to solve the problem. Full article

The gut microbiota plays a critical role in chronic kidney disease (CKD) and hypertension. Trimethylamine-N-oxide (TMAO) and trimethylamine (TMA) are gut microbiota-derived metabolites, and both are known uraemic toxins that are implicated in CKD, atherosclerosis, colorectal cancer and cardiovascular risk. Therefore, the detection and quantification of TMAO, which is a metabolite from gut microbes, are important for the diagnosis of diseases such as atherosclerosis, thrombosis and colorectal cancer. In this study, a new “colour-switch” method that is based on the combination of a plasma separation pad/absorption pad and polyallylamine hydrochloride-capped manganese dioxide (PAH@MnO₂) nanozyme was developed for the direct quantitative detection of TMAO in whole blood without blood sample pretreatment. As a proof of concept, a limit of quantitation (LOQ) of less than 6.7 μM for TMAO was obtained with a wide linear quantification range from 15.6 to 500 μM through quantitative analysis, thereby suggesting potential clinical applications in blood TMAO monitoring for CKD patients. Full article

More than three million patients are treated for kidney failure world-wide. Haemodialysis, the most commonly used treatment, requires large amounts of water and generates mountains of non-recyclable plastic waste. To improve the environmental footprint, dialysis treatments need to develop absorbents to regenerate the waste dialysate. Whereas conventional dialysis clears water-soluble toxins, it is not so effective in clearing protein-bound uraemic toxins (PBUTs), such as indoxyl sulfate (IS). Thus, developing absorption devices to remove both water-soluble toxins and PBUTs would be advantageous. Vapour induced phase separation (VIPS) has been used in this work to produce polycaprolactone/chitosan (PCL/CS) composite symmetric porous monoliths with extra porous carbon additives to increase creatinine and albumin-bound IS absorption. Moreover, these easy-to-fabricate porous monoliths can be formed into the required geometry. The PCL/CS porous monoliths absorbed 436 μg/g of albumin-bound IS and 2865 μg/g of creatinine in a single-pass perfusion model within 1 h. This porous PCL/CS monolith could potentially be used to absorb uraemic toxins, including PBUTs, and thus allow the regeneration of waste dialysate and the development of a new generation of environmentally sustainable dialysis treatments, including wearable devices. Full article

Chronic kidney disease (CKD) is a major public health concern that affects around 10 percent of the world’s population. The severity of CKD is mainly due to the high prevalence of cardiovascular (CV) complications in this population. The aim of this review is to describe the arterial remodelling associated with CKD, to provide a quick overview of the mechanisms involved and to review the recent pharmacological approaches aimed at improving vascular health in CKD. CKD patients are exposed to metabolic and haemodynamic disorders that may affect the CV system. Large artery functional and geometric abnormalities have been well documented in CKD patients and are associated with an increase in arterial stiffness and a maladaptive remodelling. Uraemic toxins, such as indoxyl sulphate, p-cresyl sulphate, protein carbamylation and advanced glycation products, exert various effects on vascular smooth muscle cell functions. The low-grade inflammation associated with CKD may also affect arterial wall composition and remodelling. It is worth noting that the CV risk for CKD patients remains high despite the pharmacological control of traditional CV risk factors, suggesting the need for innovative therapeutic strategies. An interventional study targeting the NLRP3 inflammasome has provided some interesting preliminary results that need to be confirmed, especially in terms of safety. Full article

Chronic kidney disease (CKD) is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with significant mortality. The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in children. Chronic itch (CI) is a common symptom appearing due to various underlying dermatological and systemic conditions. CI may also appear in association with CKD and is termed chronic kidney disease-associated itch (CKD-aI). CKD-aI is relatively well-described in the literature concerning adults, yet it also affects children. Unfortunately, the data on paediatric CKD-aI is particularly scarce. This narrative review aims to describe various aspects of CKD-aI with an emphasis on children, based on the available data in this population and the data extrapolated from adults. Its pathogenesis is described in details, focusing on the growing role of uraemic toxins (UTs), as well as immune dysfunction, altered opioid transmission, infectious agents, xerosis, neuropathy and dialysis-associated aspects. Moreover, epidemiological and clinical aspects are reviewed based on the few data on CKD-aI in children, whereas treatment recommendations are proposed as well, based on the literature on CKD-aI in adults and own experience in managing CI in children. Full article

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (−3.1% (−5.9%; −0.3%) (p = 0.035)), free p-cresyl sulfate (−2.5% (−4.7%; −0.3%) (p = 0.034)), total indole acetic acid (IAA) (−1.6% (−3.0%; −0.3%) (p = 0.020)), free IAA (−6.6% (−9.3%; −3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (−3.0% (−5.6%; −0.5%) (p = 0.021)) and free pCG levels (−3.3% (−5.8%; −0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD. Full article

In recent years, a number of groups have been investigating the use of “empty” liposomes with no drug loaded as scavengers both for exogenous intoxicants and endogenous toxic molecules. Preclinical trials have demonstrated that repurposing liposomes to sequester such compounds may prove clinically useful. The use of such “empty” liposomes in the dialysate during dialysis avoids recognition by complement surveillance, allowing high doses of liposomes to be used. The “reach” of dialysis may also be increased to molecules that are not traditionally dialysable. We aim to review the current literature in this area with the aims of increasing awareness and informing further research. A structured literature search identified thirteen papers which met the inclusion criteria. Augmenting the extraction of ammonia in hepatic failure with pH-gradient liposomes with acidic centres in peritoneal dialysis is the most studied area, with work progressing toward phase one trials. Liposomes used to augment the removal of exogenous intoxicants and protein-bound uraemic and hepatic toxins that accumulate in these organ failures and liposome-supported enzymatic dialysis have also been studied. It is conceivable that liposomes will be repurposed from the role of pharmaceutical vectors to gain further indications as clinically useful nanomedical antidotes/treatments within the next decade. Full article

Shiga toxin (Stx)-producing Escherichia coli strains are foodborne pathogens that can cause severe human diseases, such as haemorrhagic colitis and haemolytic uraemic syndrome. Stxs are encoded by bacteriophages (Stx phages) which show remarkable variations in genome composition and harbour several genes of unknown function. Recently, a gene encoding a sialate O-acetylesterase (NanS-p) was identified in some relevant Stx2a phages and it was suggested that it could provide advantages for bacterial growth in the gut. The aim of this study was to analyse the presence and sequence of nanS-p genes in available Stx2a phage genomes. A total of 59 DNA sequences of Stx2a phages were extracted from the NCBI GenBank database with the BLAST program using the stx_2a sequence from phage 933W as a query sequence, either as complete phage genomes (45) or from bacterial genomes by subsequent analysis with the PHASTER web server (14). Comparative analysis revealed that nanS-p was located downstream of stx_2a in all genomes. Twenty different amino acid sequences of NanS-p were identified. Specifically, catalytic esterase domains showed only 11 possible sequences, with differences mainly observed in nine amino acid positions. Sequences corresponding to the N-terminal domain (DUF1737) showed three possible sequences, two of them closely related, while the C-terminal domain was highly variable, with four groups with structural differences. Since sialate O-acetylesterase activity has been determined from particular Stx2a phages, new studies are necessary to evaluate if the NanS-p subtypes identified in the present study also differ in their biological activity. Full article