Indoxyl sulfate has been identified as a major factor in the dysregulation of several genes. It is classified as a poorly dialyzable uremic toxin and thus a leading cause in the poor survival rate of dialysis patients. A monocentric, prospective, open cohort study was performed in 43 male patients undergoing chronic renal replacement therapy in a single hemodialysis center. The aim of the study was to determine the influence of acetate- versus citrate-buffered dialysis fluids in hemodialysis (HD) and postdilution hemodiafiltration (HDF) settings on the elimination of indoxyl sulfate. Also, additional factors potentially influencing the serum concentration of indoxyl sulfate were evaluated. For this purpose, the predialysis and postdialysis concentration ratio of indoxyl sulfate and total protein was determined. The difference was of 1.15 (0.61; 2.10), 0.89 (0.53; 1.66), 0.32 (0.07; 0.63), and 0.44 (0.27; 0.77) μmol/g in acetate HD and HDF and citrate HD and HDF, respectively. Acetate HD and HDF were superior when concerning IS elimination when compared to citrate HD and HDF. Moreover, residual diuresis was determined as the only predictor of lower indoxyl sulfate concentration, suggesting that it should be preserved as long as possible. This trial is registered with EU PAS Register of Studies EUPAS23714.
- MeSH
- acetáty farmakologie MeSH
- dialýza ledvin metody MeSH
- dialyzační roztoky chemie farmakologie MeSH
- hemodiafiltrace metody MeSH
- hydrogenuhličitany MeSH
- indican krev farmakokinetika MeSH
- kyselina citronová krev farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin terapie MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- MeSH
- biokompatibilní materiály terapeutické užití MeSH
- dialyzační roztoky * chemie farmakologie škodlivé účinky terapeutické užití MeSH
- glukosa aplikace a dávkování metabolismus škodlivé účinky MeSH
- lidé MeSH
- peritoneální dialýza metody MeSH
- peritoneum metabolismus účinky léků MeSH
- produkty pokročilé glykace škodlivé účinky MeSH
- Check Tag
- lidé MeSH
♦ BACKGROUND: Permanent stimulation of the peritoneum during peritoneal dialysis (PD) is likely to result in increased expression of genes encoding proteins involved in inflammation and tissue remodeling. Peritoneal fibrosis and neoangiogenesis may develop. ♦ OBJECTIVE: To assess highly expressed genes potentially in volved in peritoneal alterations during PD treatment using an animal model. ♦ METHODS: A PD catheter was implanted in 36 male Wistar rats after 70% nephrectomy. The rats were divided into 3 groups, exposed to dialysis solution for 8 weeks, and sacrificed 2 weeks later. Group B was exposed to a buffer, group D was exposed to a 3.86% glucose-based dialysis solution, and in group D+H, a second hit of intraperitoneal blood on top of the dialysis solution was given to induce the development of peritoneal sclerosis. Before sacrifice, peritoneal function was assessed. Omental tissue was obtained for analysis of gene expression using RT-qPCR. ♦ RESULTS: Fibrosis scores, vessel counts, and peritoneal function parameters were not different between the groups. Genes involved in the transforming growth factor beta signaling pathway, cell proliferation, angiogenesis, and inflammation were more expressed (p < 0.05) in the D+H group. Almost no differences were found between the control groups. We identified 4 genes that were related to peritoneal transport. ♦ CONCLUSION: Already a mid-term peritoneal exposure, when no microscopical and functional alterations are present, provokes activation of gene pathways of cell proliferation, fibrosis, neoangiogenesis, and inflammation.
- MeSH
- chronické selhání ledvin terapie MeSH
- dialyzační roztoky farmakologie MeSH
- genetická transkripce * MeSH
- imunohistochemie MeSH
- interval spolehlivosti MeSH
- jehlová biopsie MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- nefrektomie metody MeSH
- patologická angiogeneze genetika MeSH
- peritoneální dialýza škodlivé účinky metody MeSH
- peritoneální fibróza genetika patologie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.
- MeSH
- akutní poškození ledvin terapie MeSH
- antikoagulancia škodlivé účinky ekonomika farmakologie MeSH
- citráty škodlivé účinky ekonomika farmakologie MeSH
- dialyzační roztoky škodlivé účinky ekonomika farmakologie MeSH
- energetický metabolismus účinky léků MeSH
- energetický příjem účinky léků MeSH
- hemodiafiltrace škodlivé účinky ekonomika metody MeSH
- heparin škodlivé účinky ekonomika farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- náklady na zdravotní péči MeSH
- prospektivní studie MeSH
- vodní a elektrolytová nerovnováha etiologie prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- diabetické nefropatie * krev terapie MeSH
- dialyzační roztoky * farmakologie terapeutické užití MeSH
- glukosa aplikace a dávkování MeSH
- glykovaný hemoglobin analýza MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- lipidy krev MeSH
- peritoneální dialýza * metody škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- komentáře MeSH
OBJECTIVE: In this study, we compared the activity of interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation and biocompatibility, and its other signaling components, the soluble IL-6 receptor (sIL-6R) and soluble Gp130 (sGp130), in peritoneal effluent from patients treated with icodextrin-based (E) peritoneal dialysis (PD) solution and glucose-based bicarbonate/lactate-buffered (P) solution. METHODS: Using baseline peritoneal ultrafiltration capacity, 33 stable incident PD patients were allocated either to P only (n = 20) or to P plus E for the overnight dwell (n = 13). We used ELISA to determine IL-6, sIL-6R, and sGp130 in timed overnight effluent at 1, 6, and 12 months after PD initiation. Flow cytometry was used to measure expression of IL-6R and Gp130 on isolated peritoneal leukocytes at the same time points. Peritonitis was an exclusion criterion. RESULTS: At all time points, levels of IL-6 and sIL-6R, and the appearance rates of IL-6 (90.5 pg/min vs. 481.1 pg/min, p < 0.001; 138.6 pg/min vs. 1187.5 pg/min, p < 0.001; and 56.1 pg/min vs. 1386.0 pg/min, p < 0.001), sIL-6R (2035.3 pg/min vs. 4907.0 pg/min, p < 0.01; 1375.0 pg/min vs. 6348.4 pg/min, p < 0.01; and 1881.3 pg/min vs. 5437.8 pg/min, p < 0.01), and sGp130 (37.6 ng/min vs. 65.4 ng/min, p < 0.01; 39.2 ng/min vs. 80.6 ng/min, p < 0.01; 27.8 ng/min vs. 71.0 ng/min, p < 0.01) were significantly higher in peritoneal effluent from E-treated patients than from P-treated patients. Expression of IL6-R and Gp130 on individual leukocyte types isolated from PD effluent did not differ between E- and P-treated patients. The numbers of white blood cells present in effluent were higher in E-treated than in P-treated patients at all time points, but no significant differences were seen in the differential counts or in the number of exfoliated mesothelial cells. The IL-6 parameters in effluent from E-treated patients correlated with their plasma C-reactive protein. Despite the increased activation of the IL-6 system, no increase in peritoneal permeability as assessed by the dialysate-to-plasma ratio of creatinine in E effluent or by systemic inflammation was observed throughout the study. CONCLUSIONS: Higher levels of IL-6, its soluble receptors, and leukocyte expression were observed in E-treated than in P-treated patients, but this difference was not associated with alterations in peritoneal permeability or systemic inflammation during 1 year of follow-up. Leukocyte counts in effluent from E-treated patients were within the normal range previously reported for glucose solutions. This lack of clinical consequences may be a result of a parallel rise in sIL-6R and sGp130, which are known to control the biologic activity of IL-6. The utility of IL-6 level determinations, in isolation, for assessing the biocompatibility of PD solutions is questionable.
- MeSH
- časové faktory MeSH
- dialyzační roztoky farmakologie MeSH
- dospělí MeSH
- ELISA MeSH
- fixní kombinace léků MeSH
- glukany farmakologie MeSH
- glukosa farmakologie MeSH
- hydrogenuhličitany farmakologie MeSH
- interleukin-6 metabolismus MeSH
- kontinuální ambulantní peritoneální dialýza metody MeSH
- kyselina mléčná farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- následné studie MeSH
- peritoneum účinky léků metabolismus patologie MeSH
- prospektivní studie MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- signální transdukce MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- analýza přežití MeSH
- biokompatibilní materiály farmakologie MeSH
- časové faktory MeSH
- chronické selhání ledvin diagnóza mortalita terapie MeSH
- dialyzační roztoky farmakologie MeSH
- dospělí MeSH
- glukosa farmakologie MeSH
- hodnocení rizik MeSH
- hodnoty glomerulární filtrace MeSH
- interval spolehlivosti MeSH
- Kaplanův-Meierův odhad MeSH
- klinické křížové studie MeSH
- koncentrace vodíkových iontů MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- peritoneální dialýza metody mortalita škodlivé účinky MeSH
- peritonitida epidemiologie chemicky indukované patofyziologie MeSH
- randomizované kontrolované studie jako téma MeSH
- referenční hodnoty MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- vyšetření funkce ledvin MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- souhrny MeSH
Together with the development of peritoneal dialysis (PD), appropriate animal models play an important role in the investigation of physiological, pathophysiological and clinical aspects of PD. However, there is still not an ideal experimental PD animal model. In this study, 45 Sprague-Dawley rats were divided into three groups. Group 1 (n=15) was receiving daily peritoneal injection through the catheter connected to the abdominal cavity, using PD solution containing 3.86 % D-glucose. Group 2 (n=15) was receiving daily peritoneal injection of 0.9 % physiological saline through a catheter. Group 3 (n=15), which was subjected to sham operation, served as controls. Our results showed that WBC counts in peritoneal effluent of Group 1 were slightly higher than those of Group 2 and control group, respectively (p<0.05). However, there was no episode of infection in any group. In addition, there was no significant difference in neutrophils fractions among these three groups. Hematoxylin-eosin and Masson's trichrome staining demonstrated a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum exposed to high glucose (Group 1) compared to Group 2 and controls (p<0.01). These data indicated that we established a novel rat model of PD with a modified catheter insertion method. This model is more practical, easy to operate, not too expensive and it will facilitate the investigate of long-term effects of PD.
- MeSH
- dialyzační roztoky farmakologie MeSH
- financování organizované MeSH
- katétry MeSH
- krysa rodu rattus MeSH
- modely u zvířat MeSH
- peritoneální dialýza metody MeSH
- peritoneum metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- uremie etiologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- antibakteriální látky aplikace a dávkování farmakologie terapeutické užití MeSH
- dialyzační roztoky farmakologie chemie škodlivé účinky MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- mikrobiologické techniky MeSH
- peritoneální dialýza metody škodlivé účinky MeSH
- peritonitida diagnóza farmakoterapie prevence a kontrola MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- směrnice pro lékařskou praxi MeSH
Současným hlavním problémem peritoneální dialýzy (PD) je progresivní zhoršování funkce peritoneální membrány (PM) v průběhu léčby PD, které vede k technickému selhání metody přibližně u 50% pacientů po 5 letech léčby. Důsledkem léčby PD jsou morfologické změny PM, mezi něž patří ztráta mezotelu, intersticiální fibróza, vaskulární skleróza a neoangiogeneze. Dále jsou uváděny patogenetické faktory poškození PM. Klinickým důsledkem morfologických a funkčních změn PM je zvýšení transportu malých solutů, které vede k rychlému vymizení osmotického gradientu glukózy a tím ke zhoršení ultrafiltrační kapacity PM. Jedním z možných řešení tohoto problému je zavedení nové generace peritoneálních dialyzačních roztoků s nižším obsahem degradačních produktů glukózy (GDP) a s neutrálním pH.
The main current challenge in peritonea dialysis (PD) is the progressive deterioration of peritoneal membrane (PM) function during PD, resulting in technical failure of the method in about 50% of patients after 5 years of therapy. PDV therapy results in PM morphological changes including mesothelial loss, interstitial fibrosis, vascular sclerosis, and neoangiogenesis. Pathogenic factors of PM injury are also identified. A clinical sequel of morphological and functional changes in PM is increased small solute transport leading to rapid elimination of the osmotic gradient of glucose and, hence, deterioration of the ultrafiltration PM capacity. A potential solution of these problems is introduction of a new generation of peritoneal dialysis solutions with a lower content of glucose degradation products (GDP) and a neutral pH.
- MeSH
- dialyzační roztoky farmakologie škodlivé účinky MeSH
- glukosa metabolismus MeSH
- iontové kanály patofyziologie MeSH
- lidé MeSH
- nemoci peritonea etiologie patofyziologie MeSH
- peritoneální dialýza škodlivé účinky MeSH
- produkty pokročilé glykace škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH