Icodextrin peritoneal dialysis (PD) solution has been shown to increase interleukin-6 (IL-6) levels in PD effluent as well as leukocyte and mesothelial cell count. Mesothelial cells release cancer antigen 125 (CA125), which is used as a marker of mesothelial cell mass. This 1-year prospective study was designed to compare peritoneal effluent cell population, its inflammatory phenotype and biocompatibility biomarkers IL-6 and CA125 between icodextrin (E) and glucose bicarbonate/lactate (P) based PD solutions. Using baseline peritoneal ultrafiltration capacity, 19 stable incident PD patients were allocated either to P only (N = 8) or to P plus E for the overnight dwell (N = 11). Flow cytometry was used to measure white blood cell count and differential and the expression of inflammatory molecules on peritoneal cells isolated from timed overnight peritoneal effluents. Compared to P, E effluent showed higher leukocyte (10.9 vs. 7.9), macrophages (6.1 vs. 2.5) and mesothelial cells (0.3 vs. 0.1)×10(6) /L count, as well as expression of HLA DR on mesothelial cells and IL-6 (320.5 vs. 141.2 pg/min) on mesothelial cells and CA125 appearance rate (159.6 vs. 84.3 IU/min), all P < 0.05. In the E group, correlation between IL-6 and CA125 effluent levels (r = 0.503, P < 0.05) as well as appearance rates (r = 0.774, P < 0.001) was demonstrated. No effect on systemic inflammatory markers or peritoneal permeability was found. Icodextrin PD solution activates local inflammation without systemic consequences so the clinical relevance of this observation remains obscure. Correlation between effluent IL-6 and CA125 suggests that CA125 might be upregulated due to inflammation and thus is not a reliable marker of mesothelial cell mass and/or biocompatibility.
- Klíčová slova
- Biocompatibility, Cancer antigen 125, Icodextrin interleukin-6, Peritoneal dialysis,
- MeSH
- antigen CA-125 metabolismus MeSH
- dialyzační roztoky chemie MeSH
- dospělí MeSH
- glukany chemie MeSH
- glukosa chemie MeSH
- hydrogenuhličitany chemie MeSH
- icodextrin MeSH
- interleukin-6 metabolismus MeSH
- laktáty chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- peritoneální dialýza metody MeSH
- počet leukocytů MeSH
- prospektivní studie MeSH
- průtoková cytometrie MeSH
- senioři MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigen CA-125 MeSH
- dialyzační roztoky MeSH
- glukany MeSH
- glukosa MeSH
- hydrogenuhličitany MeSH
- icodextrin MeSH
- interleukin-6 MeSH
- laktáty MeSH
Any degree of microinflammation is an independent risk factor for mortality for patients with chronic kidney disease in all stages. During peritoneal dialysis, intraperitoneal activation of inflammation occurs, the degree of which in stable patients without infectious complications depends in particular on the content of peritoneal dialysis solution with regard to osmotic agents (glucose, icodextrin) and buffer (lactate, bicarbonate or their combination) which as the same time defines the level of biocompatibility of these solutions. The degree of intraperitoneal inflammation affects peritoneal permeability, however there is no evidence of it directly increasing the systemic inflammation and it does not correlate with mortality. On the other hand, the systemic inflammation affected in peritoneal dialysis patients primarily by age and comorbidities, i.e. factors independent of peritoneal dialysis alone, does predict long-term clinical results.Key words: biocompatibility - icodextrin - inflammation - peritoneal dialysis - peritoneal dialysis solutions.
- MeSH
- dialyzační roztoky MeSH
- glukany MeSH
- glukosa MeSH
- hydrogenuhličitany MeSH
- icodextrin MeSH
- lidé MeSH
- peritoneální dialýza * MeSH
- peritoneum MeSH
- peritonitida * MeSH
- rizikové faktory MeSH
- zánět * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dialyzační roztoky MeSH
- glukany MeSH
- glukosa MeSH
- hydrogenuhličitany MeSH
- icodextrin MeSH
Intraperitoneal glucose degradation products (GDP) load influences systemic advanced glycation end products (AGEs) but the effects on soluble receptor for AGEs (s-RAGE) and its proinflammatory ligands: extracellular newly identified receptor for advanced glycation end-products binding protein(EN-RAGE) and high mobility group box-1 protein (HMGB-1) are unknown. We aimed to compare plasma and peritoneal s-RAGE, EN-RAGE and HMGB-1 between three peritoneal dialysis (PD) prescription regimens with different intraperitoneal GDP loads. High GDP load (glucose-lactate PD fluid, D; N = 8) was compared with a low (glucose-bicarbonate/lactate with icodextrin for overnight dwell, E; N = 9) and a very low GDP load (glucose-bicarbonate/lactate, P; N = 16). D group demonstrated higher plasma EN-RAGE, 77.8 ng/mL, vs. both E, 11.2, P < 0.001 and P, 27.0, P < 0.001 as well as higher plasma HMGB-1, 2.2 ng/mL vs. both E, 1.1, P < 0.01 and P, 1.5, P < 0.01. Plasma s-RAGE, which did not differ between D, E and P, correlated with its effluent levels. Patients with faster peritoneal transport (D/Pcr > 0.65) tended to have higher plasma s-RAGE compared to slow transporters (2300 vs. 1762 pg/mL, P = 0.056). Peritoneal clearance of s-RAGE and EN-RAGE was higher with E compared to both D and P (P < 0.001 resp. P < 0.01). Subgroup of PD patients with CRP above median demonstrated higher plasma HMGB-1 and EN-RAGE, P < 0.05 for both. A lower intraperitoneal GDP load is associated with decreased plasma levels of EN-RAGE and HMGB-1. Peritoneal transport, microinflammation and the capability of icodextrin to increase peritoneal clearance of middle molecular weight substances might also exert an effect on plasma s-RAGE and its proinflammatory ligands levels.
- Klíčová slova
- Advanced glycation end products, Extracellular newly identified receptor for advanced glycation end products-binding protein, High mobility group box-1 protein, Peritoneal dialysis, Receptor for advanced glycation end products,
- MeSH
- biologický transport fyziologie MeSH
- glukany aplikace a dávkování MeSH
- glukosa aplikace a dávkování metabolismus MeSH
- icodextrin MeSH
- lidé středního věku MeSH
- lidé MeSH
- ligandy MeSH
- mediátory zánětu metabolismus MeSH
- mladý dospělý MeSH
- peritoneální dialýza metody MeSH
- peritoneum metabolismus MeSH
- produkty pokročilé glykace metabolismus MeSH
- protein HMGB1 metabolismus MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- glukany MeSH
- glukosa MeSH
- icodextrin MeSH
- ligandy MeSH
- mediátory zánětu MeSH
- produkty pokročilé glykace MeSH
- protein HMGB1 MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické 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
- icodextrin 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
- Názvy látek
- dialyzační roztoky MeSH
- fixní kombinace léků MeSH
- glukany MeSH
- glukosa MeSH
- hydrogenuhličitany MeSH
- icodextrin MeSH
- interleukin-6 MeSH
- kyselina mléčná MeSH
Icodextrin, a glucose polymer, is an alternative osmotic agent to glucose in peritoneal dialysis solutions. Icodextrin generates ultrafiltration through colloid osmosis and is thus effective even during long-term (e.g., nighttime) dwells and in cases of high peritoneal permeability, where it prevents dialysate reabsorption into the systemic circulation. Ultrafiltration is maintained even in the presence of peritonitis. The incidence of bacterial peritonitis is not different when using icodextrin- or glucose-based solutions. Some time ago, icodextrin use was implicated in an increased incidence of sterile peritonitis. This was due to contamination of some batches of the solution by peptidoglycan present in the cell wall of G+ bacteria. Using exact isotope methods, treatment with icodextrin-based solution has been shown to improve the hydration status of peritoneal dialysis patients, suggesting a potential for improved blood pressure control. Icodextrin-based dialysis is associated with a reduction of left ventricular mass. Given the methodological flaws of trials conducted to date, the acute hemodynamic effects of icodextrin cannot be conclusively interpreted. Inclusion of icodextrin-based solution instead of the glucose-based one into the prescription of peritoneal dialysis decreases the metabolic load with glucose potentially having a beneficial effect on hyperlipidemia, hyperinsulinemia and hyperleptinemia, with improved glycemic control in patients with diabetes as an additional benefit. Function of the peritoneum as a dialysis membrane is stable during icodextrin-based treatment, possibly longer compared with glucose-based solutions. Data derived from a large-scale registry have shown lower mortality oficodextrin-treated patients; this, however, needs to be confirmed by prospective randomized controlled trials.
- MeSH
- glukany * škodlivé účinky MeSH
- glukosa * škodlivé účinky MeSH
- hemodialyzační roztoky * škodlivé účinky MeSH
- hemodynamika MeSH
- icodextrin MeSH
- lidé MeSH
- peritoneální dialýza * MeSH
- peritoneum metabolismus MeSH
- peritonitida etiologie MeSH
- ultrafiltrace MeSH
- vodní a elektrolytová rovnováha MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- glukany * MeSH
- glukosa * MeSH
- hemodialyzační roztoky * MeSH
- icodextrin MeSH
- MeSH
- glukany * MeSH
- glukosa * MeSH
- hemodialyzační roztoky * MeSH
- icodextrin MeSH
- lidé MeSH
- peritoneální dialýza * MeSH
- peritoneum metabolismus MeSH
- ultrafiltrace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- komentáře MeSH
- úvodníky MeSH
- Názvy látek
- glukany * MeSH
- glukosa * MeSH
- hemodialyzační roztoky * MeSH
- icodextrin MeSH
- MeSH
- chronické selhání ledvin terapie MeSH
- dialyzační roztoky farmakologie MeSH
- glukany farmakologie MeSH
- glukosa farmakologie MeSH
- icodextrin MeSH
- leptin metabolismus MeSH
- lidé MeSH
- peritoneální dialýza metody MeSH
- peritoneální dutina patofyziologie MeSH
- peritoneum účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- dialyzační roztoky MeSH
- glukany MeSH
- glukosa MeSH
- icodextrin MeSH
- leptin MeSH
BACKGROUND: To date, peritoneal dialysis has been performed almost exclusively using dialysis solutions containing glucose as the osmotic agent. Use of these solutions is fraught with problems regarding adequate fluid removal from the body and is also associated with undesirable metabolic effects; hence the search for alternative osmotic agents. A dialysis solution with the glucose polymer icodextrin generates ultrafiltration on the principle of colloidal osmosis. The aim of the study was to establish the effect of icodextrin-base dialysis solution on the magnitude of ultrafiltration and evaluate selected metabolic parameters of patients treated by ambulatory peritoneal dialysis. METHODS AND RESULTS: A total of 9 patients whose glucose-based solution was replaced by an icodextrin-based solution during the night-time exchange were evaluated. A control group of 9 patients used glucose-solution during all exchanges. Night-time bag ultrafiltration, blood pressure, and the serum levels of lipids, insulin, leptin, maltose, and amylase were determined before icodextrin administration (time 0), at one-month intervals (time 1, 2, 3), and one month after study completion (time 4). In icodextrin-treated patients, ultrafiltration rose from 246.5 +/- 60.5 ml (mean +/- SEM) at time 0 to 593.1 +/- 87.4 ml; p < 0.01, at time 1, to 547 +/- 67 ml; p < 0.05, at time 2, and to 586.7 +/- 58.8 ml; p < 0.01, at time 3, the icodextrin administration led to a rise in maltose from 0.02 +/- 0.01 g/l at time 0 to 0.1 +/- 0.1 g/l; p < 0.01, at time 1, to 1.0 +/- 0.09 g/l; p < 0.01, at time 2, and to 1.1 +/- 0.09 g/l; p < 0.01, at time 3, with a fall to zero values at time 4 (NS). Icodextrin administration was followed by a decrease in leptinemia from 34.6 +/- 17.2 ng/ml at time 0 to 21.7 +/- 8.9 ng/ml; p < 0.05, at time 1, to 21.4 +/- 9.5 ng/ml; p < 0.05, at time 2, and to 15.9 +/- 24.1 ng/ml; p < 0.05 at time 4. Insulin and lipid levels were not affected. There was no change in the above parameters in the control group. Icodextrin-treated patients reduced their antihypertensive medication, but not statistically significantly. CONCLUSION: Icodextrin administration significantly increase ultrafiltration thus providing for effective control of hydration status without the need for high-level glucose-based dialysis solutions. The use of a glucose polymer-based dialysis solution is associated with a significant yet reversible rise in serum maltose. The decrease in leptin may signal a reduction in body weight after replacing glucose in dialysis solutions with icodextrin, or enhanced rates of leptin elimination as a result of ultrafiltration-induced convective transport.
- MeSH
- chronické selhání ledvin krev patofyziologie terapie MeSH
- dialyzační roztoky * MeSH
- dospělí MeSH
- glukany * MeSH
- glukosa * MeSH
- icodextrin MeSH
- kontinuální ambulantní peritoneální dialýza * MeSH
- krevní tlak MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy krev MeSH
- maltosa krev MeSH
- senioři MeSH
- ultrafiltrace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dialyzační roztoky * MeSH
- glukany * MeSH
- glukosa * MeSH
- icodextrin MeSH
- leptin MeSH
- lipidy MeSH
- maltosa MeSH