peritoneal membrane Dotaz Zobrazit nápovědu
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
Při peritoneální dialýze je jako dialyzační membrána využíváno peritoneum. Skrz peritoneum probíhá odstraňování solutů a nadbytečné vody. Transport látek se děje hlavně difúzí, se zvětšující se molekulovou hmotností nabývá významu transport konvektivní. Přesun se děje přes systém pórů. Dle tzv. třípórové teorie je voda transportována ultramalými kanály - aquaporiny. Voda s malými soluty je dále transportována tzv. malými póry a makromolekuly póry velkými. 44% vodního transportu zajišťují aquaporiny. porucha jejich funkce je jednou z důležitých příčin ultrafiltračního selhání. Proto je při určování charakteristik peritonea kladen stále větší důraz na vyšetření funkce aquaporinů. Modifikovaný PET test je jednou z alternativ původního PET testu, lehce proveditelný v klinické praxi a poskytující doplňující informace týkající se nejen základních charakteristik peritoneální membrány, ale i ultrafiltrační kapacity a možnosti detekce ultrafiltračního selhání.
In peritoneal dialysis the peritoneum is used as a dialysis membrane. It is involved in the removal of excess water and waste products from the circulation to the peritoneal cavity. The movement of solutes from blood to dialysate is the result of diffus ive and convective transport. The convection becomes increasingly more important the higher the molecular weight of solute. The three pore model theory is used to describe water transport. Low molecular weight solutes and water pass across small pores , the transport of macromolecules occurs through large pores. The third set of pores – ultrasmall pores ( aquaporins), are due to their extremely small size exclusively permeable to water , and not to solutes. Aquaporins are responsible for 44% of fluid removal, alteration of their function is one of the causes of ultrafiltration failure. The modified PET is the periton eal equilibration test adapted for analysis of ultrafiltration failure. The test gives besides characteristics of peritoneal membra ne function more accurate information on net ultrafiltration, is feasible in routine clinical practice.
♦ 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
BACKGROUND AND OBJECTIVES: Phosphate control impacts dialysis outcomes. Our aim was to define peritoneal phosphate transport in peritoneal dialysis (PD) and to explore its association with hyperphosphatemia, phosphate clearance (PPhCl), and PD modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred sixty-four patients (61% on continuous ambulatory PD [CAPD]) were evaluated at month 12. PPhCl was calculated from 24-hour peritoneal effluent. Phosphate (Ph) and creatinine (Cr) dialysate/plasma (D/P) were calculated at a 4-hour 3.86% peritoneal equilibration test. RESULTS: D/PPh correlated with D/PCr. PPhCl correlated better with D/PPh than with D/PCr. Prevalence of hyperphosphatemia (>5.5 mg/dl) was 30%. In a multiple regression analysis, only residual renal function was independently, negatively associated with hyperphosphatemia; in anuric patients, only D/PPh was an independent factor predicting hyperphosphatemia. D/PPh was 0.57 ± 0.10, and according to this, 16% of the patients were fast, 31% were fast-average, 35% were slow-average, and 17% were slow transporters. PPhCl was 37.5 ± 11.7 L/wk; it was lower in the slow transporter group (31 ± 14 L/wk). Among fast and fast-average transporters, PPhCl was comparable in both PD modalities. In comparison to automated PD, CAPD was associated with increased PPhCl among slow-average (36 ± 8 versus 32 ± 7 L/wk) and slow transporters (34 ± 15 versus 24 ± 9 L/wk). CONCLUSIONS: In hyperphosphatemic, particularly anuric, patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate phosphate control on automated PD.
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
- MeSH
- glukany MeSH
- glukosa MeSH
- hemodialyzační roztoky MeSH
- lidé MeSH
- peritoneální dialýza MeSH
- peritoneum metabolismus MeSH
- ultrafiltrace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- recenze MeSH
- úvodníky 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
