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Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Online hemodiafiltration (Ol-HDF) and expanded hemodialysis (HDx; using medium cut-off dialyzers) have shown superior removal of diverse uremic toxins, particularly middle molecules and inflammatory cytokines, compared to conventional hemodialysis (HD). However, the relative efficacy of toxin removal between HDx and Ol-HDF remains unclear. This study aimed to compare these two techniques. A randomized controlled trial was conducted among thrice-weekly hemodialysis patients. Participants were randomized into either a post-dilution Ol-HDF group or an HDx group using two types of medium cut-off dialyzers (Theranova 500 ® and Elisio HX21 ® ) over 8 weeks. Efficacy was assessed by reduction ratios (RR) and pre-dialysis toxin levels. Statistical analysis used T-tests and generalized estimating equations. A total of 40 patients were enrolled (mean age 64.6 ± 12.0 years; 82.5% male; dialysis vintage 53.4 ± 38.0 months). The Ol-HDF group, with a mean convection volume of 24.7 L, had significantly higher RR for beta-2 microglobulin (82.8% vs. 74.6%; p  < 0.001), parathyroid hormone (80.4% vs. 60.6%; p  = 0.007), homocysteine (58.0% vs. 50.0%; p  = 0.009), and kappa- and lambda-free light chains (73.3% vs. 64.6%; p  = 0.0001 and 62.5% vs. 52.0%; p  = 0.0026, respectively). Pre-dialysis toxin levels at the end of the study were similar between groups. These findings highlight that Ol-HDF demonstrated superior removal of uremic toxins, while HDx was comparable to Ol-HDF in maintaining pre-dialysis levels of middle molecules and inflammatory cytokines. Trial registration This study was registered in the Thai Clinical Trials Registry (TCTR) on the first posted date 10/02/2023 with the registration number TCTR20230210004.

Background Pruritus is a common skin symptom manifesting with an unpleasant sensation and desire to itch and scratch. Pruritis can be a hallmark of many skin diseases as well as other non cuatneous diseases. Aim of the study To compare the efficacy of gabapentin versus narrow band UVB versus combination of both in treatment of uremic pruritus. Methods This study that included 60 patients diagnosed with uremic pruritus, randomly allocated into one of three groups. Group A received oral gabapentin 300 mg OD for six weeks, group B received NB-UVB phototherapy three times per week in nonconsecutive days for a total of 18 sessions (6 weeks) and group C received combination of both therapies for 6 weeks. Efficacy was assessed by visual analogue scale (VAS) and 5-D itch scale before and after the end of therapy. Results Significant difference of VAS score between groups A & C ( P  = 0.029) and between group B & C ( P  = 0.027) was demonstrated. Complete responders represented 55% of group C (combination treatment group), 20% of group A & only 15% of group B. The highest frequency of no response was detected for group A (30%) followed by group B (15%) and lowest for group C (5%). Conclusion Combination of both gabapentin and NB-UVB is a promising medication for the treatment of uremic pruritus. Further well-designed clinical and experimental studies are needed to clarify the relationship between the frequency of NB-UVB phototherapy sessions and gabapentin dosing for an optimal response.

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Background Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes’ severity and quality of life. Methods In this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: 1) the exercise training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months. Restless Legs Syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by Dual Energy X Ray Absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires. Results Exercise training and dopamine agonists were effective in reducing syndrome’s symptoms by 46% (P = 0.009) and 54% (P = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (P < 0.05), however, only the dopamine agonists significantly improved sleep quality (P = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (P = 0.014), which also reduced fat infiltration in muscles (P = 0.044) and improved physical performance (P > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (P = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (P = 0.016). Conclusions A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS. Trial registration NCT00942253

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.

Home hemodialysis, despite its recognized clinical benefits such as improved cardiac health and enhanced quality of life, remains underutilized worldwide. This study aims to evaluate the efficacy of home hemodialysis within slow daily dialysis programs, employing the Physidia S3 monitor. A prospective trial was conducted with 16 stable patients suffering from end-stage kidney disease and undergoing home hemodialysis. The study assessed the efficiency of slow daily short treatment dialysis using diverse criteria, including percent reduction, effective clearances, and solute mass removal, across a broad spectrum of uremic compounds, including sodium. Controlled sessions were implemented to replicate daily home treatment conditions. Selecting urea and ß2M as key biomarkers due to their associations with patient outcomes, our study achieved a standardized weekly Kt/V of 2.26 [1.99–2.70] and estimated kidney urea clearance of 11.4 [10.9–12.4] mL/min. ß2M mass removal per session was 146 mg, extrapolating to 707 (×5) and 845 (×6) mg weekly. Additionally, the time-averaged concentration of ß2M was maintained at 19.4 mg/L. The study also identified a net sodium mass removal of 126 mmol [98–182] or 7.4 g [5.8–10.7] NaCl per session. In conclusion, our findings suggest that slow daily, short treatment time, high flux hemodialysis, augmented by enhanced internal convective clearance, represents a highly efficient renal replacement modality on a weekly basis across large molecular weight uremic compounds. Moreover, the solute dialysate saturation coefficient emerges as a promising marker in slow-flow settings.

The platelet-to-lymphocyte ratio (PLR) has been used as a marker of inflammation, endothelial damage, and a predictor of mortality. Expanded hemodialysis (HDx) using medium cut-off dialyzer (MCO) can effectively clear medium-sized uremic toxins. This study evaluated the effect of the Theranova dialyzer, a type of MCO dialyzer, on PLR and uremia-related inflammatory markers. A total of 44 patients with maintenance hemodialysis (HD) using high-flux dialyzer were randomly allocated to the Theranova or high-flux group. PLR and inflammatory markers including fibroblast growth factor 23, tumor necrosis factor-α (TNF-α), and interleukin 6 were evaluated every 4 weeks. The changes in PLR and the reduction ratio of inflammatory markers were compared between two groups during the 12-week study period. The baseline characteristics and PLR were not different between groups. After 12 weeks, the levels of PLR, and TNF-α were significantly lower in the Theranova group compared to the high-flux group (all p < 0.05). The generalized estimating equation model also revealed a significant decrease in PLR over time in the Theranova group than in the high-flux group (p = 0.04). The fold change in 12-week PLR to baseline PLR was lower in the Theranova group than in the high-flux group (p = 0.03). In the multivariable linear regression analysis, the Theranova dialyzer showed a negative correlation with the PLR fold change (β = −0.32, p = 0.04). Our results showed that HDx using the Theranova dialyzer improves PLR over time compared to the high-flux HD. The superior removal of the inflammatory uremic toxins by the Theranova dialyzer may have reduced inflammation and inflammation-related complications in HD patients.

Modern hemodialysis employs weak acids as buffers to prevent bicarbonate precipitation with calcium or magnesium. Acetate, the most used acid, is linked to chronic inflammation and poor dialysis tolerance. Citrate has emerged as a potential alternative, though its effect on dialysis efficiency is not clear. This study aims to compare the efficacy of acetate- and citrate-based dialysates, focusing on protein-bound uremic toxins and dialysis doses. This single-center prospective crossover study includes prevalent patients participating in a thrice-weekly online hemodiafiltration program. Four dialysates were tested: two acetate-based (1.25 and 1.5 mmol/L calcium) and two citrate-based (1.5 mmol/L calcium with 0.5 and 0.75 mmol/L magnesium). Pre- and post-dialysis blood samples of eighteen patients were analyzed for urea, creatinine, p-cresyl sulfate, indoxyl sulfate, and albumin. Statistical significance was assessed using paired t-tests and repeated measures of ANOVA. There were no significant differences in dialysis dose (Kt), urea, creatinine, or indoxyl sulfate reduction ratios between acetate- and citrate-based dialysates. However, a significant decrease in the reduction ratio of p-cresyl sulfate was observed with the acetate dialysate containing 1.25 mmol/L calcium and the citrate dialysate with 0.5 mmol/L magnesium compared to the acetate dialysate containing 1.5 mmol/L calcium and the citrate dialysate with 0.75 mmol/L magnesium (51.56 ± 4.75 and 53.02 ± 4.52 vs. 65.25 ± 3.38 and 58.66 ± 4.16, p 0.007). No differences in dialysis dose were found between acetate- and citrate-based dialysates. However, citrate dialysates with lower calcium and magnesium concentrations may reduce the albumin displacement of p-cresyl sulfate. Further studies are needed to understand the observed differences and optimize the dialysate composition for the better clearance of protein-bound uremic toxins.