Hemodiafiltration (HDF) is increasingly used because of its enhanced theoretical clearance of diverse uremic toxins, particularly middle molecules and inflammatory cytokines, relative to conventional hemodialysis (HD), yet evidence on its biochemical benefits remains conflicting. Therefore, this meta-analysis was performed to evaluate the effects of HDF versus HD on uremic toxins, inflammation, anemia, and nutritional parameters. A systematic literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials to identify relevant studies. Only randomized controlled trials (RCTs) were included. Random-effects meta-analyses were performed to evaluate changes in the prespecified outcomes. Twenty-four RCTs involving 6072 dialysis patients were included. Compared with conventional HD, HDF was associated with significant reductions in serum phosphorus (weighted mean difference [WMD] −0.28 mg/dL; 95% CI −0.44 to −0.12) and β2-microglobulin (WMD −4.84 mg/dL; 95% CI −6.13 to −3.54). HDF also significantly reduced serum urea and C-reactive protein (CRP) levels, along with weekly erythropoietin requirements. Serum albumin levels were slightly but significantly lower in the HDF group than in the conventional HD group (WMD –0.06 g/dL; 95% CI −0.10 to −0.01); however, the clinical significance of such a difference remains uncertain. Higher convective volumes were identified as a key determinant of greater reductions in β2-microglobulin and CRP. Compared with conventional HD, HDF demonstrated superior reductions in several surrogate endpoints, including serum phosphorus, urea, β2-microglobulin, CRP, and weekly erythropoietin requirements. Reduced need for phosphate binders and anemia management may lower treatment-related costs.

CKD, nutrition and the brain: How to maintain brain health through nutrition in CKD.

Rising numbers of organ failures have intensified the demand for high-performance biomaterials to support the development of bioartificial organs and advanced bioreactors. Hollow fiber membranes (HFMs) are particularly well-suited for such applications, including bioartificial kidney, liver, and 3D cell culture systems, due to their unique architecture and functional versatility. In this study, we engineered HFMs by blending amphiphilic Pluronic F127 (PF127) with poly(ether sulfone) (PES), aiming to enhance both separation efficiency and cellular attachment and proliferation. Physicochemical characterization revealed that PF127 incorporation resulted in a concentric, porous membrane structure with significantly improved porosity as compared to that of plain PES HFMs. Biocompatibility was assessed using human embryonic kidney (HEK293) and hepatocellular carcinoma liver (HepG2) cell lines. Confocal microscopy, MTT cell viability assays, flow-cytometry-based live/dead assays, and calcein AM/propidium iodide staining demonstrated that PF127/PES HFMs strongly support the attachment and proliferation of viable cells. The attached cells exhibited high metabolic activity and formed three-dimensional spheroids, indicating the bioactive influence of PF127. Hemocompatibility evaluation by hemolysis and terminal complement complex (SC5b9) showed that the HFMs fabricated were hemocompatible, suggesting a diminished inflammatory response. Additionally, separation performance evaluation demonstrated a high ultrafiltration coefficient, highest for 2.5 PF127 (173.83 ± 7.31 mL m-2 h-1 mmHg-1) and efficient removal of a broad range of uremic toxins, including urea, creatinine, macroglobulin analogs, and protein-bound toxins such as indoxyl sulfate. Collectively, the enhanced cytocompatibility with kidney and liver cells, hemocompatibility, and separation capability of PF127/PES HFMs make them promising scaffolds for bioartificial kidney and liver applications.

Protein-bound uremic toxins are inefficiently cleared by dialysis and contribute to complications in chronic kidney disease, motivating approaches that target their gut-derived precursors. Here we investigate anaerobic p-cresol metabolism by the environmental denitrifier Thauera aminoaromatica S2, a pathway originally evolved for aromatic pollutant degradation. Proteomic stable isotope probing with 13 C-labeled p-cresol reveals strong incorporation of labeled carbon into T. aminoaromatica proteins, whereas parallel incubations with human fecal microbiomes show minimal incorporation, indicating limited intrinsic gut capacity for p-cresol utilization. Label-enriched proteins enable reconstruction of the anaerobic p-cresol degradation pathway and identification of key enzymes synthesized during growth on p-cresol. Moreover, hydrogel-encapsulated T. aminoaromatica remains active during co-incubation with the gut microbiome, achieving complete removal of 0.3 mM p-cresol in less than 10 hours, a timescale compatible with typical intestinal transit in the colon. Together, these findings establish a biochemical basis for repurposing environmental aromatic degradation pathways for gut-localized p-cresol removal.

ABSTRACT Chronic kidney disease (CKD) is projected to become the fifth most prevalent chronic disease globally. Establishing a reliable animal model is essential for advancing prevention and treatment strategies. In this study, we compared CKD mice induced by four adenine‐containing diets: 0.2% or 0.25% adenine in conventional or purified feed. All diets significantly elevated serum urea nitrogen and creatinine levels, causing renal damage, and disrupted gut microbiota and metabolic function. Notably, the group receiving the 0.2% adenine purified diet displayed the most severe renal lesions and uniquely developed hyperphosphatemia and hypercalcemia, which are hallmarks of mineral bone disorder and indicate an increased cardiovascular risk in advanced CKD. Gut microbiota alterations included a reduction in Akkermansia ( p < 0.01), and enriched Lactobacillus ( p < 0.05). Metabolic pathway analysis revealed significant upregulation of phenylalanine, tyrosine, and tryptophan biosynthesis ( p < 0.01) in the 0.2% purified diet group which linked to uremic toxin production. Overall, the 0.2% adenine purified diet induces a comprehensive, reproducible, and clinically relevant CKD model, ideal for studying pathophysiological mechanisms and evaluating therapeutic interventions.

Indoxyl sulfate (IS), one of protein bound uremic toxins (PBUTs), is associated with various complications in chronic kidney disease (CKD) patients and could partially be removed through hemodialysis and hemoperfusion due to its high affinity to HSA. Many studies have demonstrated the potential for blood purification, such as poly-β-cyclodextrin (PCD) and metal-organic frameworks (MOFs), providing new possibilities for the efficient removal of IS. Here, we utilized β-cyclodextrin (β-CD)-grafted polyethyleneimine (PEI), which is referred to as βP, as a scavenger for IS and sodium alginate (SA) as the matrix material to prepare alginate-based hybrid macrospheres (MS). The surface polydopamine (PDA) and argatroban (AG) modification resulted in enhanced biocompatibility and anticoagulation. The results indicated that the hybrid MS demonstrated effective absorption and removal capacity (79.96 %) of IS. Moreover, the lower hemolysis rate (0.36 %) and longer anticoagulation-related factors (APTT: 161.5 s; TT, 35.6 s) also revealed favorable biocompatibility and anticoagulation. This study presents a new way to designate blood purification materials and highlights their potential in clinical hemoperfusion treatment.

Background: Cardiovascular disease remains the primary cause of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Conventional risk factors fail to fully explain the high prevalence of resistant hypertension and intradialytic hemodynamic instability in this population. Emerging evidence points to the degradation of the endothelial glycocalyx (eGC), a protective luminal layer regulating vascular tone and permeability. Syndecan-1 (SDC-1), a core component of the eGC, sheds into the circulation during vascular stress. This study aimed to synthesize evidence regarding the magnitude of dialysis-induced SDC-1 shedding and its validity as a prognostic biomarker for survival and vascular stiffness. M ethods: We conducted a systematic review and associative meta-analysis of observational studies and clinical trials. We searched Scopus, PubMed, and Web of Science for studies quantifying serum SDC-1 in HD patients and relevant physiologic comparators. Data were stratified to analyze three domains: the second hit phenomenon (acute pre- vs. post-dialysis shedding), diagnostic correlations with pulse wave velocity (PWV) and fluid status, and prognostic hazard ratios (HR) for all-cause mortality. A random-effects model was employed to account for population heterogeneity, specifically stratifying hemodialysis cohorts from heart failure comparators. Results: Ten pivotal studies involving over 1,500 patients were included. The analysis confirmed a substantial acute surge in serum SDC-1 post-hemodialysis (Standardized Mean Difference = 1.24, p < 0.001), indicating that the dialysis procedure actively injures the endothelium. Elevated baseline SDC-1 correlated significantly with arterial stiffness (PWV) and sodium overload, supporting a mechanism of salt-induced vascular stiffening. In prognostic analysis, high SDC-1 was a robust independent predictor of mortality (Pooled HR = 1.65, 95% CI: 1.12–2.43). Conclusion: Hemodialysis acts as a vascular stressor, triggering acute shedding of the endothelial glycocalyx. This shedding is mechanistically linked to sodium dysregulation and vascular stiffness, independent of traditional uremic toxins. SDC-1 serves as a valuable prognostic marker for endothelial health and survival, suggesting a need for endothelium-protective dialysis strategies.

Hemodialysis, the principal therapy for end-stage renal disease (ESRD), directly influences pulmonary mechanics by alleviation of fluid overload and uremic toxin accumulation. Hemodialysis (HD), the main renal replacement therapy, removes excess volume and solutes, but its acute effects on pulmonary function remain uncertain. This meta-analysis evaluates impact of hemodialysis on pulmonary function and examines pre-to post-dialysis changes in spirometric parameters among ESRD patients. We conducted meta-analysis of cross-sectional studies that measured pulmonary function in ESRD patients on maintenance hemodialysis. Data from 16 eligible studies (n = 719 patients) were synthesized. Our analysis was focused on changes in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, forced expiratory flow at 25%-75% (FEF25-75), and peak expiratory flow rate (PEFR). Statistical analysis was performed using random-effects models to calculate pooled mean differences (MD) for spirometric outcomes. Hemodialysis was associated with significant improvements in percent-predicted FEV1 (+8.99%) and FVC(+12.87%), while absolute changes in these parameters were small and not statistically significant. The FEV1/FVC ratio and PEFR also improved in percent-predicted terms. Sensitivity analyses confirmed stability of results, though high heterogeneity (I2>75%) was observed for several outcomes. Publication bias was minimal, with Egger's and Begg's tests indicating no significant asymmetry, except for borderline Begg's p-value for FVC (%pred). These improvements likely reflect ultrafiltration-mediated relief of pulmonary congestion and modulation of uremic milieu. Hemodialysis acutely mitigates renal failure-related pulmonary restriction, with percent-predicted spirometry showing consistent gains. These effects highlight role of dialysis prescriptions and fluid management strategies in optimizing respiratory as well as renal outcomes.

Objective: To propose a physiology-based, creatinine-guided dosing strategy for furosemide administration in critically ill patients with acute decompensated heart failure (ADHF), acute kidney injury (AKI), or chronic kidney disease (CKD), integrating renal function into diuretic decision-making to optimize safety and efficacy. Data Sources: Relevant literature was identified through searches of PubMed, Embase, and Scopus using the terms furosemide, loop diuretics, diuretic resistance, organic anion transporters, creatinine, and renal dysfunction. Key randomized and mechanistic studies, including the DOSE, Furosemide Stress Test, ADVOR, PUSH-AHF, and ENACT-HF trials, were reviewed. Data Synthesis: Furosemide efficacy depends on its active tubular secretion via organic anion transporters (OAT1/3). In renal dysfunction, secretion is reduced, uremic toxins compete for transport, and diuretic resistance ensues. Empiric high-dose bolus therapy, common in practice, often leads to suboptimal response or toxicity. A physiologically derived dosing framework is proposed in which the minimum daily dose of furosemide (mg) equals serum creatinine (mg/dL × 88), applicable up to 5 mg/dL. This rule reflects the relationship between creatinine, tubular drug delivery, and the pharmacodynamic threshold for antidiuresis. Conclusions: Serum creatinine serves as a practical surrogate for furosemide delivery to its site of action. The proposed creatinine-guided dosing rule provides a rational, individualized approach to diuretic therapy that may improve decongestion efficacy while reducing risk of renal and electrolyte complications in critically ill patients. Keywords: Furosemide, Loop diuretics, Acute decompensated heart failure, Acute kidney injury, Chronic kidney disease, Diuretic resistance, Creatinine-guided dosing, Critical care

Microbiota-targeted modulation of the gut-kidney axis in diabetic kidney disease: Therapeutic advances and future perspectives.

P-cresol, indole and indole-3-acetic acid (IAA) are catabolites of amino acids, formed by the gut microbiome. Most of these aromatic hydrocarbon derivatives are excreted by the colon before reentering the body to form “exogenous” protein-bound uremic toxins (PBUTs), which aggravate chronic kidney disease (CKD). Removal efficiencies of these PBUT precursors from model phosphate-buffered saline solutions by three different surface-modified nanoporous carbon adsorbents (PCs) were studied. PCs were produced by physicochemical and/or acid base activation of carbonized rice husk waste. Removal rates achieved values of 32–96% within a 3 h contact time. High micro/mesoporosity and surface chemistry of the N- and P-doped biochars were established by N2 adsorption studies, SEM/EDS analysis, XPS and FT-IR-spectroscopy. The ammoxidized PC-N1 had the highest adsorption capacity (1.97 mmol/g for IAA, 2.43 mmol/g for p-cresol and 2.42 mmol/g for indole), followed by “urea-nitrified” PC-N2, whilst the phosphorylated PC-P demonstrated the lowest adsorption capacity for these solutes. These results do not correlate with the total pore volume values for PC-N2 (0.91 cm3/g) < PC-P (1.56 cm3/g) < PC-N1 (1.84 cm3/g), suggesting that other parameters such as the micropore volume (PC-N1 > PC-N2 > PC-P) and the interaction of surface chemical functional groups with the solutes play key roles in the adsorption mechanism. N-doped PC-N1 and PC-N2 have basic functional groups with higher affinity with acidic IAA and p-cresol. The ion-exchange mechanism of phenolic and indolic compound chemisorption by nanoporous carbon adsorbents, modified with surface N- and P-containing functional groups, has been proposed.

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.

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice.

Hypertension is a major global health challenge, with excessive dietary salt intake recognized as a key environmental factor contributing to its pathogenesis. However, safe and effective dietary interventions for salt-sensitive hypertension remain limited. Vine tea (Ampelopsis grossedentata), a traditional herbal tea widely consumed for centuries in southern China, has been reported to exhibit antioxidant, anti-inflammatory, and hepatoprotective activities, yet its antihypertensive efficacy and underlying mechanisms remain unclear. In this study, the chemical profile of vine tea aqueous extract (VTE) was characterized by UPLC-Q-TOF-MS, identifying dihydromyricetin, isoquercitrin, and myricetin as the predominant flavonoids. The protective effects of VTE were evaluated in C57BL/6J mice with high-salt-diet (HSD)-induced hypertension. VTE treatment significantly lowered systolic blood pressure and ameliorated cardiac and renal injury, accompanied by reduced inflammation, fibrosis, and cardiac stress-related gene expression. Gut microbiota analysis using 16S rRNA gene sequencing revealed that VTE restored microbial richness and diversity, enriching short-chain fatty acid-producing taxa while suppressing pathogenic Desulfovibrio and Ruminococcus torques. Untargeted plasma metabolomic profiling based on UPLC-Q-TOF-MS further showed that VTE normalized tryptophan, bile acid, and glycerophospholipid metabolism, decreasing the uremic toxin indoxyl sulfate while increasing tauroursodeoxycholic acid. Notably, these protective effects were abolished under antibiotic-induced microbiota depletion, confirming that VTE acts through a gut microbiota-dependent mechanism. Collectively, VTE mitigates salt-induced hypertension and cardiorenal injury by remodeling the gut microbiota-metabolite axis, supporting its potential as a natural dietary intervention for managing hypertension.

Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut-kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid-producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut-kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice.

Differences in gut microbiota composition are an important reason for lower serum p-cresol sulfate levels in anuric peritoneal dialysis patients compared to hemodialysis patients

A clinical impact of apoptosis inhibitor of macrophage on feline chronic kidney disease.

To compare the efficacy of, as well as effects on micro-inflammatory and metabolic acidosis between high-flux and low-flux dialysis in the hemodialysis population. This multicenter retrospective cohort study, based on pre-defined blood sample data completeness criteria, screened and included treatment records of 187 patients undergoing high-flux dialysis and 189 patients undergoing low-flux dialysis from 2016 to 2018. Ultimately, 374 dialysis sessions meeting the completeness criteria from the high-flux group and 378 sessions from the low-flux group were included in the analysis. Baseline characteristics, clinical tolerance, dialysis efficiency, serum laboratory parameters, micro-inflammatory status, and metabolic acidosis indicators were compared between the two groups. Both groups exhibited good biocompatibility, with effective removal of excess water and uremic toxins from the body. Contrastingly, high-flux dialysis was better than low-flux dialysis in removing moderate and small molecule toxins, maintaining blood pressure and acid-base balance in the body. The study provides useful insights into the comparative efficacy, micro-inflammation, and metabolic acidosis of high-flux and low-flux dialysis. These findings support the preferential use of high-flux dialysis to enhance solute clearance and correct acidosis, while affirming that both modalities are well-tolerated. The choice should be individualized based on patient characteristics and treatment goals.

New insights in the chronic kidney disease-associated osteoarthritis progression: Role of uremic toxin indoxyl sulfate-induced chondrocyte senescence and ferroptosis.

Sodium nitroprusside improves ischemia-induced neovascularization via the HO-1/NOX and AKT/eNOS signaling pathways in chronic kidney disease.