Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is the most important functional change, and peritoneal fibrosis is the major morphological alteration. Both are caused by the continuous exposure to dialysis solutions that are different from plasma water with regard to the buffer substance and the extremely high-glucose concentrations. Glucose has been incriminated as the major cause of long-term peritoneal membrane changes, but the precise mechanism has not been identified. We argue that glucose causes the membrane alterations by peritoneal pseudohypoxia and by the formation of advanced glycosylation end products (AGEs). After a summary of UF kinetics including the role of glucose transporters (GLUT), and a discussion on morphologic alterations, relationships between function and morphology and a survey of the pathogenesis of UF failure (UFF), it will be argued that impaired UF is partly caused by a reduction in small pore fluid transport as a consequence of AGE-related vasculopathy and - more importantly - in diminished free water transport due to pseudohypoxia, caused by increased peritoneal cellular expression of GLUT-1. The metabolism of intracellular glucose will be reviewed. This occurs in the glycolysis and in the polyol/sorbitol pathway, the latter is activated in case of a large supply. In both pathways the ratio between the reduced and oxidised form of nicotinamide dinucleotide (NADH/NAD+ ratio) will increase, especially because normal compensatory mechanisms may be impaired, and activate expression of hypoxia-inducible factor-1 (HIF-1). The latter gene activates various profibrotic factors and GLUT-1. Besides replacement of glucose as an osmotic agent, medical treatment/prevention is currently limited to tamoxifen and possibly Renin/angiotensis/aldosteron (RAA) inhibitors.

• MeSH
• dialyzační roztoky škodlivé účinky   metabolismus   MeSH
• glukosa škodlivé účinky   metabolismus   MeSH
• glykosylace MeSH
• lidé MeSH
• peritoneální dialýza * škodlivé účinky   MeSH
• peritoneum metabolismus   MeSH
• ultrafiltrace MeSH
• voda metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. METHODS: Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry. RESULTS: While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD. CONCLUSIONS: Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.

• MeSH
• chronické selhání ledvin * chirurgie   metabolismus   MeSH
• dialýza ledvin MeSH
• dialyzační roztoky metabolismus   MeSH
• dítě MeSH
• glukosa metabolismus   MeSH
• lidé MeSH
• peritoneální dialýza * škodlivé účinky   MeSH
• peritoneum metabolismus   MeSH
• peritonitida * metabolismus   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Several studies have been published in the last decade on the effects of low glucose degradation product (GDP) neutral pH (L-GDP/N-pH) dialysis solutions on peritoneal morphology and function during the long-term PD treatment. Compared to conventional solutions, the impact of these solutions on the morphological and functional alterations of the peritoneal membrane is discussed, including those of effluent proteins that reflect the status of peritoneal tissues. Long-term PD with conventional solutions is associated with the loss of mesothelium, submesothelial and interstitial fibrosis, vasculopathy, and deposition of advanced glycosylation end products (AGEs). L-GDP/N-pH solutions mitigate these alterations, although vasculopathy and AGE deposition are still present. Increased vascular density was found in some studies. Small solute transport increases with PD duration on conventional solutions. Initially, higher values are present on L-GDP/N-pH treatment, but these may be reversible and remain stable with PD duration. Consequently, ultrafiltration (UF) is lower initially but remains stable thereafter. At 5 years, UF and small pore fluid transport are higher, while free water transport decreased only slightly during follow-up. Cancer antigen 125 was initially higher on L-GDP/N-pH solutions, suggesting better mesothelial preservation but decreased during follow-up. Therefore, L-GDP/N-pH solutions may not prevent but reduce and retard the peritoneal alterations induced by continuous exposure to glucose-based dialysis fluids.

• MeSH
• dialyzační roztoky metabolismus   MeSH
• glukosa metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• peritoneální dialýza * škodlivé účinky   MeSH
• peritoneum metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.

• MeSH
• dialyzační roztoky škodlivé účinky   metabolismus   MeSH
• glukosa škodlivé účinky   metabolismus   MeSH
• hypoxie MeSH
• lidé MeSH
• NAD * metabolismus   MeSH
• peritoneální dialýza * škodlivé účinky   MeSH
• peritoneum metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Peritoneal dialysis (PD) is one of the methods of renal replacement therapy. The continuous exposure of peritoneal membrane to bio-incompatible PD solutions leads to the development of morphological and functional abnormalities of the peritoneum. Permanent stimulation of peritoneum results in increased expression of genes encoding proteins involved in inflammation and tissue remodeling. This leads in release of cytokines, pro-inflammatory, pro-fibrotic and growth factors, which are present in peritoneal effluent of PD patients and contribute to peritoneal fibrosis and neoangiogenesis. In addition, this process leads to alterations of peritoneal membrane and is one of the main causes of membrane failure. The aim of the study is to demonstrate a difference in peritoneal expression of genes involved in activation of pro-inflammatory and pro-fibrotic pathways between short- and longterm PD patients. Furthermore, to analyse the relationship between gene expression, effluent cytokines, growth factors level on one hand and solute and fluid transport parameters changes on the other.

Peritoneální dialýza (PD) je významnou metodou chronické náhrady funkce ledvin. V důsledku dlouhodobé expozice peritoneální membrány bio-inkompatibilním dialyzačním roztokům dochází k morfologickým a funkčním změnám peritonea ovlivňujícím úspěch léčby. Odpovědí na neustálou stimulaci peritonea je zvýšená exprese některých genů kódujících proteiny účastnící se zánětu a remodelace tkáně vedoucí k uvolňování cytokinů, růstových faktorů a dalších zánětlivých působků, nacházejících se v dialyzátu peritoneálně dialyzovaných pacientů a podílejících se na peritoneální fibroze a angiogenezi. To vše přispívá k alteraci peritoneální membrány a je jednou z hlavních příčin jejího selhání. Cílem projektu je sledovat rozdíl mezi peritoneální expresí genů aktivujících alteraci cytokinů, růstových faktorů mezi krátkodobě a dlouhodobě léčenými PD pacienty. Dále analyzovat vztah mezi mezi peritoneální expresí genů, hladinou cytokinů, růstových faktorů, zánětlivých působků a časovým vývojem změn transportu solutů a tekutin přes peritoneální membránu v závislosti na délce trvání PD léčby.

• MeSH
• cytokiny genetika   MeSH
• dialyzační roztoky škodlivé účinky   MeSH
• exprese genu MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• peritoneální dialýza škodlivé účinky   MeSH
• permeabilita buněčné membrány genetika   účinky léků   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• genetika, lékařská genetika
• nefrologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

• MeSH
• chronické selhání ledvin diagnóza   terapie   MeSH
• dialýza ledvin škodlivé účinky   metody   MeSH
• hemodialyzační roztoky škodlivé účinky   chemie   MeSH
• hydrogenuhličitany krev   MeSH
• lidé MeSH
• parathormon krev   MeSH
• sekundární hyperparatyreóza etiologie   patofyziologie   MeSH
• senzitivita a specificita MeSH
• vápník krev   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH

In standard care, hemodialysis patients are often treated with a center-specific fixed dialysate sodium concentration, potentially resulting in diffusive sodium changes for patients with plasma sodium concentrations below or above this level. While diffusive sodium load may be associated with thirst and higher interdialytic weight gain, excessive diffusive sodium removal may cause intradialytic symptoms. In contrast, the new hemodialysis machine option "Na control" provides automated individualization of dialysate sodium during treatment with the aim to reduce such intradialytic sodium changes without the need to determine the plasma sodium concentration. This proof-of-principle study on sodium control was designed as a monocentric randomized controlled crossover trial: 32 patients with residual diuresis of ≤1000 mL/day were enrolled to be treated by high-volume post-dilution hemodiafiltration (HDF) for 2 weeks each with "Na control" (individually and automatically adjusted dialysate sodium concentration) versus "standard fixed Na" (fixed dialysate sodium 138 mmol/L), in randomized order. Pre- and post-dialytic plasma sodium concentrations were determined at bedside by direct potentiometry. The study hypothesis consisted of 2 components: the mean plasma sodium change between the start and end of the treatment being within ±1.0 mmol/L for sodium-controlled treatments, and a lower variability of the plasma sodium changes for "Na control" than for "standard fixed Na" treatments. Three hundred seventy-two treatments of 31 adult chronic hemodialysis patients (intention-to-treat population) were analyzed. The estimate for the mean plasma sodium change was -0.53 mmol/L (95% confidence interval: [-1.04; -0.02] mmol/L) for "Na control" treatments and -0.95 mmol/L (95% CI: [-1.76; -0.15] mmol/L) for "standard fixed Na" treatments. The standard deviation of the plasma sodium changes was 1.39 mmol/L for "Na control" versus 2.19 mmol/L for "standard fixed Na" treatments (P = 0.0004). Whereas the 95% CI for the estimate for the mean plasma sodium change during "Na control" treatments marginally overlapped the lower border of the predefined margin ±1.0 mmol/L, the variability of intradialytic plasma sodium changes was lower during "Na control" versus "standard fixed Na" treatments. Thus, automated dialysate sodium individualization by "Na control" approaches isonatremic dialysis in the clinical setting.

• MeSH
• algoritmy MeSH
• chronické selhání ledvin terapie   MeSH
• dialýza ledvin metody   MeSH
• dialyzační roztoky chemie   terapeutické užití   MeSH
• individualizovaná medicína metody   MeSH
• klinické křížové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• sodík chemie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

Electrodialysis (ED) is frequently used in the desalination of whey. However, the fouling onto the membrane surface decreases the electrodialysis efficiency. Pulsed Electrodialysis Reversal (PER), in which short pulses of reverse polarity are applied, is expected to decrease the fouling onto membrane surface during ED. Three (PER) regimes were applied in the desalination of acid whey (pH ≤ 5) to study their effects on the membrane fouling and the ED efficiency. The PER regimes were compared to the conventional ED as the control. For each regime, two consecutive runs were performed without any cleaning step in-between to intensify the fouling. After the second run, the membranes were subjected to the Scanning electron microscope (SEM) imaging and contact angle measurement to investigate the fouling on the membrane surface in different regimes. The ED parameters in the case of conventional ED were almost the same in the first and the second runs. However, the parameters related to the ED efficiency including ED capacity, ash transfer, and ED time, were deteriorated when the PER regimes were applied. The contact angle values indicated that the fouling on the diluate side of anion exchange membranes was more intensified in conventional ED compared to the PER regimes. The SEM images also showed that the fouling on the diluate side of both cation and anion exchange membranes under PER regimes was reduced in respect to the conventional ED. However, the back transfer to the diluate compartment when the reverse pulse was applied is dominant and lowers the ED efficiency slightly when the PER is applied.

• MeSH
• dialýza metody   MeSH
• dialyzační roztoky chemie   MeSH
• elektrochemie MeSH
• membrány umělé MeSH
• mikroskopie elektronová rastrovací MeSH
• povrchové vlastnosti MeSH
• soli chemie   MeSH
• syrovátka chemie   MeSH
• Publikační typ
• časopisecké články MeSH

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

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

• MeSH
• biopsie MeSH
• chronické selhání ledvin terapie   MeSH
• dialyzační roztoky chemie   toxicita   MeSH
• dítě MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• fibróza MeSH
• glukosa metabolismus   MeSH
• kojenec MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• mladiství MeSH
• peritoneální dialýza škodlivé účinky   MeSH
• peritoneum krevní zásobení   účinky léků   patologie   MeSH
• peritonitida chemicky indukované   patologie   MeSH
• předškolní dítě MeSH
• studie případů a kontrol MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH