Search Results (27)

Background: Chronic kidney disease (CKD) is characterised by a disrupted gut–kidney axis, wherein intestinal dysbiosis is associated with the accumulation of uraemic toxins and the potential depletion of beneficial short-chain fatty acids (SCFAs). Whilst acetate, propionate, and butyrate are known to modulate systemic inflammation and blood pressure, their precise circulating concentrations across different CKD stages and age groups remain poorly defined. This systematic review and meta-analysis aimed to quantify blood SCFA concentrations in CKD patients compared to healthy controls. Methods: We conducted a systematic search of Medline, EMBASE, and the Cochrane Library for clinical studies reporting blood SCFA concentrations in humans with CKD. Methodological quality was assessed using the NIH tool. Standardised mean differences (SMDs) were calculated for the quantitative meta-analysis, with subgroup analyses performed for age, CKD stage, and treatment modality (dialysis vs. transplantation). Results: Twenty-one studies encompassing 9661 participants were included. Quantitative synthesis revealed a significant and consistent systemic depletion of circulating acetate and propionate in adult CKD patients compared to healthy controls (p < 0.05). This depletion followed a stage-dependent trajectory, worsening alongside declining glomerular filtration rates. Notably, a “butyrate paradox” was identified in paediatric cohorts; whilst adults showed progressive butyrate depletion, children with CKD often maintained or exhibited elevated levels, particularly in the context of hypertension. Furthermore, whilst haemodialysis patients exhibited the most profound SCFA deficiencies, kidney transplantation appeared to partially restore these metabolites toward healthy baseline levels. Conclusions: CKD is associated with a profound systemic reduction in acetate and propionate, supporting the model of a compromised gut–kidney axis based on converging evidence. The divergent results for butyrate in paediatric versus adult populations suggest that SCFA metabolism is influenced by age-related factors or compensatory mechanisms. These findings highlight the potential for SCFA monitoring as a candidate or emerging markers for detecting early renal damage and stratifying risk. Full article

Background: Dietary fibre has been increasingly recognised for its potential role in modulating inflammation, gut-derived uraemic toxins, nutritional status, and kidney-related outcomes in chronic kidney disease (CKD), particularly through mechanisms involving the gut–liver–kidney axis. While nutritional management in CKD has traditionally focused on protein intake, despite growing evidence supporting soluble and insoluble types, the role of dietary fibre remains insufficiently reflected in clinical guidelines. Objective: This systematic review evaluated the effects of dietary fibre intake on inflammatory markers, gut-derived uraemic toxins, nutritional status, kidney function, and mechanistic pathways relevant to gut–liver–kidney axis among CKD patients. Methods: PubMed, Scopus and Medline Complete were searched for observational and interventional human studies. Review articles and animal studies were excluded. A total of 45 met eligibility criteria. Risk-of-bias (RoB) was assessed using domain-based tools, and findings were synthesised narratively across predefined outcome domains. Results: Higher fibre intake was generally associated with reductions in interleukin-6 (IL-6) and selective improvements in inflammatory tone including Tumor Necrosis Factor alpha (TNF-α), while effects on C-reactive protein (CRP) varied. Several fermentable fibres were frequently linked with reduced gut-derived uraemic toxins, including indoxyl sulphate (IS), p-cresyl sulphate (pCS), and less consistently trimethylamine-N-oxide (TMAO). Nutritional markers such as albumin, BMI and overall diet quality were typically maintained or improved. Kidney function was stable across short-term interventions, with suggestions of slower decline in longer studies incorporating fibre-rich dietary patterns. Mechanistic studies frequently reported increased saccharolytic activity and favourable changes in fermentation profiles. Despite growing evidence, soluble fibre remains an underrepresented component in CKD dietary guidelines, warranting further high-quality interventional studies to confirm its therapeutic potential. Full article

Background: Patients with kidney failure requiring dialysis experience a high burden of vaccine-preventable diseases, and vaccine hypo-responsiveness is a key contributor. Uraemic toxins and gut dysbiosis are potential causes of hypo-responsiveness. Aim: This study aimed to determine whether uraemic toxin concentrations or gut dysbiosis are associated with vaccine response in haemodialysis patients. Methods: This was a single centre, observational cohort study of maintenance dialysis patients receiving a conventional 2-dose primary COVID-19 vaccination course. Demographic, clinical and vaccination data were collected from the eMR. Vaccine response (Elecsys Anti-SARS-CoV-2 immunoassay), serum uraemic toxin concentrations (indoxyl sulphate, p-cresyl sulphate, and trimethylamine N-oxide by liquid chromatography), and stool microbiome (16S rRNA gene sequencing) were measured 8 weeks after the second dose of vaccine. Results: Forty participants (43% female, mean age 66 years; 59% Caucasian) were included, 70% of whom were classified as a vaccine responder. Antibiotic exposure, prednisolone use and lymphopenia were significantly associated with hypo-responsiveness. Microbiome profiling identified differences in beta diversity between responders and non-responders, positively correlated with short-chain fatty acid producers (Parabacteriodes) and negatively with pathobionts (Escherichia/Shigella). Differential abundance analysis identified lower levels of Tyzzerella, Gemmiger, and Hungatella and higher levels of Turicibacter in vaccine responders. Total uraemic toxin burden and individual toxin concentrations did not differ between responders and hypo-responders (all p > 0.05). Stratification by low versus high/very high toxin burden groupings was not associated with response (p > 0.99). Conclusions: Differences in gut microbial composition were observed between vaccine responder groups, while uraemic toxin concentrations were not associated with vaccine responsiveness. These findings suggest gut microbiota composition may contribute to vaccine hypo-responsiveness in individuals receiving dialysis and warrant further investigation in larger mechanistic studies. Full article

Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1–CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated β-galactosidase activity, and activated phosphorylated ERK1/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD. Full article

Nephrotoxin-mediated kidney injury is an important clinical problem, as it can lead to acute kidney injury and chronic kidney disease. Both entities are associated with significant morbidity, increased hospitalisation, healthcare utilisation, and cardiovascular mortality. With the loss of kidney function, there is an accumulation of uraemic toxins, of which the protein-bound toxins—indoxyl sulphate and p-cresyl sulphate—can further inflict damage to the kidneys and the cardiovascular system, culminating in a vicious cycle. Therefore, it is imperative that clinicians have a firm understanding of the common causes and mechanisms of toxin-mediated kidney injury, as well as their clinical presentations and histopathologic features, in order to reduce the prevalence of this pernicious condition. Full article

Aim: To explore the associations between protein-bound uraemic toxins (PBTs), fibre intake and patient-focused outcomes in patients on kidney replacement therapy. Background: Despite removal of small water-soluble uraemic toxins, dialysis patients continue to experience high morbidity and mortality. Recent evidence suggests strong associations between PBTs and poorer patient outcomes and symptom burden. Reducing the generation of PBTs by increasing dietary fibre may be an alternate approach to better patient outcomes. Method: This was a cross-sectional study of haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant patients to determine the associations between uraemic toxins [p-cresyl sulfate (PCS) and indoxyl sulfate (IS)], fibre intake and patient-focused outcomes, incorporating the Integrated Palliative Outcome Scale-Renal (IPOS-renal) and EQ-5D-5L to determine symptom burden and quality of life, while physical capacity was determined using the timed up and go(TUG) test and handgrip strength (HGS). Results: Ninety participants completed the study (n = 30 in each group). There was a correlation between PBTs and the IPOS-renal score, where higher toxin levels were associated with a higher symptom burden. This was the strongest for PCS, where the significance remained after accounting for age and co-morbidities (p < 0.05). Higher PBT levels were also associated with lower HGS (p < 0.05). There was a negative correlation between fibre intake and PBTs, serum PCS (r = −0.36, p < 0.05) and serum IS (r = −0.27, p < 0.05). Lower fibre intake was also associated with a higher symptom burden measured by the IPOS-renal (p < 0.05). Transplant patients consistently performed better, with a reduced symptom burden and improved physical ability compared to dialysis patients. Conclusion: PBTs were associated with symptom burden, and lower physical ability was associated with both PBTs and patient-focused outcomes, and this needs to be further investigated in larger studies. Full article

Implementation of molecular detection methodology of Shiga toxin-producing Escherichia coli (STEC) in Danish patients began in 1997. Since then, changes in molecular detection methods and diagnostic criteria have led to the present situation, in which almost all diarrhoeal stool specimens are examined for STEC. Whole genome sequencing (WGS) of STEC isolates referred to the national reference laboratory has increased the detailed characterisation, and revealed a large spectrum, of STEC types, including cross-over pathotypes typically associated with extraintestinal disease or traveller’s diarrhoea. Association of subtype stx2a (and stx2d) with the risk of developing haemolytic uraemic syndrome (HUS) was confirmed. These changes have resulted in an increase in the number of diagnosed STEC cases from 31 cases in 1997 to 1432 in 2023. Similar increases in Europe have also been recorded. Culture of STEC is, on the other hand, declining, which poses a challenge to the identification of multiple STEC infections and outbreaks. Syndromic (PCR) test panels have also resulted in an increase in the detection of multiple microorganisms. Double or triple infections have increased the role of clinical microbiologists in interpreting and assessing the significance of diagnostic results and have also increased the need for high-quality curation of surveillance data. Full article

Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article

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