Peritoneal Accumulation of Age and Peritoneal Membrane Permeability

2000 ◽  
Vol 20 (4) ◽  
pp. 452-460 ◽  
Author(s):  
Min Sun Park ◽  
Hyon Ah Lee ◽  
Won Suk Chu ◽  
Dong Ho Yang ◽  
Seung Duk Hwang
Keyword(s):  
Membrane Permeability ◽  
High Glucose ◽  
Diabetic Patients ◽  
Peritoneal Membrane ◽  
Exit Site Infection ◽  
Peritoneal Tissue ◽  
Ultrafiltration Failure ◽  
Peritoneal Permeability ◽  
Dialysis Solutions

Background In continuous ambulatory peritoneal dialysis (CAPD), the peritoneal membrane is continuously exposed to high-glucose-containing dialysis solutions. Abnormally high glucose concentration in the peritoneal cavity may enhance advanced glycosylation end-product (AGE) formation and accumulation in the peritoneum. Increased AGE accumulation in the peritoneum, decreased ultrafiltration volume, and increased peritoneal permeability in long-term dialysis patients have been reported. Aim The purpose of the study was to evaluate the relation between peritoneal membrane permeability and peritoneal accumulation of AGE. Methods Peritoneal membrane permeability was evaluated by peritoneal equilibration test (PET) using dialysis solutions containing 4.25% glucose. Serum, dialysate, and peritoneal tissue levels of AGE were measured by ELISA method using polyclonal anti-AGE antibody. Peritoneal biopsy was performed during peritoneal catheter insertion [new group (group N), n = 18] and removal [long-term group (group LT), n = 10]. Peritoneal catheters were removed due to exit-site infection not extended into the internal cuff ( n = 6) and ultrafiltration failure ( n = 4) after 51.6 ± 31.5 months (13 – 101 months) of dialysis. PET data obtained within 3 months after the initiation of CAPD or before catheter removal were included in this study. Ten patients in group N and 4 patients in group LT were diabetic. Patients in group LT were significantly younger (46.5 ± 11.1 years vs 57.5 ± 1.3 years) and experienced more episodes of peritonitis (3.5 ± 2.1 vs 0.2 ± 0.7) than group N. Results Peritoneal tissue AGE level in group LT was significantly higher than in group N, in both nondiabetic (0.187 ± 0.108 U/mg vs 0.093 ± 0.08 U/mg of hydroxyproline, p < 0.03) and diabetic patients (0.384 ± 0.035 U/mg vs 0.152 ± 0.082 U/mg of hydroxyproline, p < 0.03), while serum and dialysate levels did not differ between the groups in both nondiabetic and diabetic patients. Drain volume (2600 ± 237 mL vs 2766 ± 222 mL, p = 0.07) and D4/D0 glucose (0.229 ± 0.066 vs 0.298 ± 0.081, p < 0.009) were lower, and D4/P4 creatinine (0.807 ± 0.100 vs 0.653 ± 0.144, p < 0.0001) and D1/P1 sodium (0.886 ± 0.040 vs 0.822 ± 0.032, p < 0.0003) were significantly higher in group LT than in group N. On linear regression analysis, AGE level in the peritoneum was directly correlated with duration of CAPD ( r = 0.476, p = 0.012), number of peritonitis episodes ( r = 0.433, p = 0.0215), D4/P4 creatinine ( r = 0.546, p < 0.027), and D1/P1 sodium ( r = 0.422, p = 0.0254), and inversely correlated with drain volume ( r = 0.432, p = 0.022) and D4/D0 glucose ( r = 0.552, p < 0.0023). AGE level in the peritoneal tissue and dialysate were significantly higher in diabetics than in nondiabetics in group LT, while these differences were not found in group N. Serum AGE level did not differ between nondiabetics and diabetics in either group N or group LT. Drain volume and D4/D0 glucose were lower and D4/P4 creatinine and D1/P1 sodium higher in diabetics than in nondiabetics in both groups. Conclusion Peritoneal accumulation of AGE increased with time on CAPD and number of peritonitis episodes, and was directly related with peritoneal permeability. Peritoneal AGE accumulation and peritoneal permeability in diabetic patients were higher than in nondiabetic patients from the beginning of CAPD.

Analysis of Non Enzymatic Glycosylation In Vivo: Impact of Different Dialysis Solutions

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 68-74 ◽  
Author(s):  
Marja M. Ho-Dac-Pannekeet ◽  
Miriam F. Weiss ◽  
Dirk R. De Waart ◽  
P. Erhard ◽  
Johan K. Hiralall ◽  
...  
Keyword(s):  
Peritoneal Membrane ◽  
Long Term Effects ◽  
Subsequent Formation ◽  
Protein Clearance ◽  
Ultrafiltration Failure ◽  
Glucose Exposure ◽  
Dialysis Solutions ◽  
Enzymatic Glycosylation

Background Glucose-containing dialysis solutions in peritoneal dialysis (PC) patients induce non enzymatic glycosylation (NEG) within the peritoneal cavity. The subsequent formation of advanced glycosylation endproducts (AGEs) may be implicated in the functional deterioration of the peritoneal membrane in long-term PC patients. Aim of the Study and Parameters Measurement of NEG by the determination of percent glycation of albumin and IgG (GP), and of AGEs by measuring pentosidine content of protein in 4-hour effluents (Peff) and serum. Subjects In 5 patients each, a comparison was made between 3.86% glucose and 1.36% glucose (GP and Peff), and between 3.86% glucose and 7.5% icodextrin (Peff). Nine patients with clinically severe ultrafiltration failure (UFF) were compared to nine patients treated with PC for 1 month. Six of the patients with UFF were treated with non glucose dialysis solutions and Peff was studied again after 6 weeks. Results No difference was found between Peff comparing 3.86% glucose to either 1.36% glucose or icodextrin. GP were higher in 3.86% glucose than in 1.36%. Glycatedlnon glycated (G/NG) protein clearance ratios were 1.29 for albumin and 1.12 for IgG (p = 0.003). In contrast to GP, both Peff and serum pentosidine were higher in the UFF patients than in the recently started patients. Peff, but not GP, correlated with duration of PC (r = 0.67, p = 0.04). In 5 of 6 patients treated with non glucose dialysate, Peff decreased while serum pentosidine was stable. .Discussion: These data show that 4-hour Peff contents are not influenced by glucose concentration or osmolality, in contrast to GP. The relation between Peff and duration of PC, and the effect of non glucose dialysate on Peff, suggest that long-term glucose exposure is an important determinant of membrane glycosylation. Thus Peff probably reflects the long-term effects of intraperitoneal glycosylation of peritoneal membrane proteins. Treatment with non glucose dialysis solutions may result in “washout” of glycosylated proteins from the peritoneal membrane.

scholarly journals Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane

2004 ◽  
Vol 66 (3) ◽  
pp. 1257-1265 ◽  
Author(s):  
Siska Mortier ◽  
Dirk Faict ◽  
Casper G. Schalkwijk ◽  
Norbert H. Lameire ◽  
A.N.S. De Vriese
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions

Monitoring of Long-Term Peritoneal Membrane Function

2001 ◽  
Vol 21 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Simon J. Davies
Keyword(s):  
Peritoneal Dialysis ◽  
Solute Transport ◽  
Water Transport ◽  
Drop Out ◽  
Published Data ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Technique Survival ◽  
Ultrafiltration Failure

Objective Peritoneal membrane function influences dialysis prescription and clinical outcome and may change with time on treatment. Increasingly sophisticated tools, ranging from the peritoneal equilibration test (PET) to the standard permeability analysis (SPA) and personal dialysis capacity (PDC) test, are available to the clinician and clinical researcher. These tests allow assessment of a number of aspects of membrane function, including solute transport rates, ultrafiltration capacity, effective reabsorption, transcellular water transport, and permeability to macromolecules. In considering which tests are of greatest value in monitoring long-term membrane function, two criteria were set: those that result in clinically relevant interpatient differences in achieved ultrafiltration or solute clearances, and those that change with time in treatment. Study Selection Clinical validation studies of the PET, SPA, and PDC tests. Studies reporting membrane function using these methods in either long-term (5 years) peritoneal dialysis patients or longitudinal observations (> 2 years). Data Extraction Directly from published data. Additional, previously unpublished analysis of data from the Stoke PD Study. Results Solute transport is the most important parameter. In addition to predicting patient and technique survival at baseline, there is strong evidence that it can increase with time on treatment. Whereas patients with initially high solute transport drop out early from treatment, those with low transport remain longer on treatment, although, over 5 years, a proportion develop increasing transport rates. Ultrafiltration capacity, while being a composite measure of membrane function, is a useful guide for the clinician. Using the PET (2.27% glucose), a net ultrafiltration capacity of < 200 mL is associated with a 50% chance of achieving less than 1 L daily ultrafiltration at the expense of 1.8 hypertonic (3.86%) exchanges in anuric patients. Using a SPA (3.86% glucose), a net ultrafiltration capacity of < 400 mL indicates ultrafiltration failure. While there is circumstantial evidence that, with time on peritoneal dialysis, loss of transcellular water transport might contribute to ultrafiltration failure, none of the current tests is able to demonstrate this unequivocally. Of the other membrane parameters, evidence that interpatient differences are clinically relevant (permeability to macro-molecules), or that they change significantly with time on treatment (effective reabsorption), is lacking. Conclusion A strong case can be made for the regular assessment by clinicians of solute transport and ultrafiltration capacity, a task made simple to achieve using any of the three tools available.

Pattern of Peritoneal Permeability in Continuous Ambulatory Peritoneal Dialysis Patients in Brunei

2003 ◽  
Vol 23 (2_suppl) ◽  
pp. 11-13
Author(s):  
Ranganathan Dwarakanathan ◽  
Hjh Zarah Yaakob ◽  
Hasnani Hadi
Keyword(s):  
Patient Population ◽  
Diabetic Patients ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Peritoneal Equilibration Test ◽  
Permeable Membrane ◽  
Brunei Darussalam ◽  
Patients With Diabetes ◽  
Peritoneal Permeability ◽  
Different Populations

Objective Peritoneal permeability may be dissimilar in different populations. The present study identified the pattern of peritoneal permeability in continuous ambulatory dialysis (CAPD) patients treated at the Department of Renal Medicine, RIPAS Hospital, Brunei Darussalam. Methods Data were collected from patients on CAPD in 2001 ( n = 65). Four children were excluded from the study. The remaining 61 patients underwent a 4-hour peritoneal equilibration test (PET) as prescribed by Twardowski et al. For those patients, adequacy of dialysis (Kt/V) was estimated. A retrospective analysis of the peritoneal membrane characteristics of those CAPD patients was also conducted. The membrane characteristics were compared with the urea clearance results. Results Of the 61 patients, 40 were non diabetic, and 21 (34.43%) were diabetic. More than half of our patients (55.74%) had membranes classified as high-average, followed by low-average (22.95%), high (18.03%), and low (3.28%). When the patient population was grouped separately into non diabetic and diabetic patients, peritoneal permeability differed between the groups ( p = 0.000585). No relationship was observed between weekly Kt/V and transport characteristics in the group with diabetes ( p = 0.219306), the group without diabetes ( p = 0.74179), or the entire patient population ( p = 0.376832) Conclusion We conclude that peritoneal permeability among Bruneian CAPD patients is probably different from that among patients from other regions of Asia (more than half of our Bruneian patients had a peritoneal membrane classified as high average). We believe that the observed difference may be related to a difference in ethnicity. In general, patients with diabetes have a highly permeable membrane. Adequacy of dialysis had no correlation to PET results in our study. A larger prospective study is required to confirm our findings.

Effects of Bicarbonate/Lactate Solution on Peritoneal Advanced Glycosylation End-Product Accumulation

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 33-38 ◽  
Author(s):  
Min Sun Park ◽  
Jin Kook Kim ◽  
Cliff Holmes ◽  
and Miriam F. Weiss
Keyword(s):  
Peritoneal Cavity ◽  
High Glucose ◽  
Parietal Peritoneum ◽  
Control Group ◽  
Normal Male ◽  
Plasma Urea ◽  
Conventional Solution ◽  
Dialysis Solutions ◽  
Advanced Glycosylation

Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague–Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However, B/L solution failed to lower pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at 2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was significantly higher in the Lac and B/L groups than in the control group. Intra-peritoneal volume was significantly higher in the B/L group than in the Lac group; D2/D0 glucose and D2/P2 urea did not differ between the two groups. In conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L solution showed a small but statistically significant protective effect against decreasing ultrafiltration as compared with Lac solution. The B/L solution attenuated peritoneal AGE accumulation compared with conventional solution, but did not affect peritoneal pentosidine levels. These findings indicate that biochemical kinetics of various AGE peptides are not unique, but multivalent.

Overnight Mesothelial Cell Exfoliation: A Magic Tool for Predicting Future Ultrafiltration Failure in Patients on Continuous Ambulatory Peritoneal Dialysis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 107-113
Author(s):  
Talerngsak Kanjanabuch ◽  
Monchai Siribamrungwong ◽  
Rungrote Khunprakant ◽  
Sirigul Kanjanabuch ◽  
Piyathida Jeungsmarn ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Nutrition Status ◽  
Continuous Exposure ◽  
Peritoneal Membrane ◽  
Dialysis Solution ◽  
Ultrafiltration Failure

⋄ Background Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. ⋄ Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were reevaluated 1 year later. ⋄ Results The numbers of total and apoptotic mesothelial cells were 0.19 ± 0.19 million and 0.08 ± 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate–to–initial dialysate (D/D0) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cutoff of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D0 glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. ⋄ Conclusions The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.

Glycated Albumin in Serum and Dialysate of Patients on Continuous Ambulatory Peritoneal Dialysis

1993 ◽  
Vol 84 (6) ◽  
pp. 619-626 ◽  
Author(s):  
E. Lamb ◽  
W. R. Cattell ◽  
A. Dawnay
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Glucose Concentration ◽  
Glycated Albumin ◽  
Protein Glycation ◽  
Structural Proteins ◽  
Diabetic Patients ◽  
Peritoneal Membrane ◽  
Membrane Function ◽  
Ultrafiltration Failure

1. Chronic use of hyperosmolar glucose solutions in continuous ambulatory peritoneal dialysis may cause glycation of peritoneal structural proteins which could contribute to membrane dysfunction and ultrafiltration failure. To determine whether glycation can occur in the environment of the dialysate, we have carried out studies using albumin as a model protein. 2. Glycated albumin was measured in the serum and dialysate of 46 patients on continuous ambulatory peritoneal dialysis (31 non-diabetic patients, 15 diabetic patients). Dialysate and serum glycated albumin (ranges 1.0-12.7% and 0.9-10.2%, respectively) were related to each other (r = 0.988, P <0.001), but dialysate glycated albumin was significantly higher than serum glycated albumin (P <0.0001), with the dialysate to serum glycated albumin ratio being greater than unity in 76% of patients (mean ratio 1.14). This implies either preferential transfer of glycated albumin across the peritoneal membrane or intraperitoneal glycation during the dwell period. 3. In vitro, significant glycation occurred in dialysate during a 6 h incubation period (P <0.01) at a rate related to the glucose concentration in the dialysate (rs = 0.63, P <0.05). The glycation rate was not significantly affected (P = 0.05) by factors other than the glucose concentration. 4. Our results demonstrate that protein glycation occurs within the peritoneum during continuous ambulatory peritoneal dialysis. Further studies are required to establish the relationship of glycation of structural proteins in the peritoneal membrane to membrane function.

scholarly journals Volume Stress-Induced Peritoneal Endothelin-1 Release in Continuous Ambulatory Peritoneal Dialysis

1999 ◽  
Vol 10 (12) ◽  
pp. 2585-2590
Author(s):  
STANISLAO MORGERA ◽  
SIMONE KUCHINKE ◽  
KLEMENS BUDDE ◽  
ANDREAS LUN ◽  
BERTHOLD HOCHER ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Endothelin 1 ◽  
Target Values ◽  
Ultrafiltration Failure ◽  
Significant Difference ◽  
The Impact ◽  
Volume Stress

Abstract. In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 ± 1023 fmol for the 1500 ml versus 6062 ± 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 ± 969 fmol versus 6124 ± 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.

scholarly journals Vascular Endothelial Growth Factor Is Essential for Hyperglycemia-Induced Structural and Functional Alterations of the Peritoneal Membrane

2001 ◽  
Vol 12 (8) ◽  
pp. 1734-1741 ◽  
Author(s):  
AN S. DE VRIESE ◽  
RONALD G. TILTON ◽  
CLIFFORD C. STEPHAN ◽  
NORBERT H. LAMEIRE
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
High Glucose ◽  
Microvascular Dysfunction ◽  
Vascular Endothelial ◽  
Peritoneal Membrane ◽  
Long Term Treatment ◽  
Glucose Exposure ◽  
Endothelial Growth Factor

Abstract. Long-term peritoneal dialysis is associated with the development of functional and structural alterations of the peritoneal membrane. Long-term exposure to the high glucose concentrations in conventional peritoneal dialysate has been implicated in the pathogenesis of peritoneal hyperpermeability and neoangiogenesis. Vascular endothelial growth factor (VEGF) is an endothelial-specific growth factor that potently stimulates microvascular permeability and proliferation. High glucose exposure upregulates VEGF expression in various cell types and tissues. This study investigated whether VEGF plays a pathogenetic role in hyperglycemia-induced microvascular dysfunction in the peritoneal membrane. The peritoneal microcirculation of streptozotocin-induced diabetic rats and age-matched controls was studiedin vivowith a combination of functional and morphologic techniques. The diabetic microcirculation was characterized by an elevated transport of small solutes, indicating the presence of an increased effective vascular surface area. The leakage of FITC-albumin was more rapid in diabetic vessels, suggesting hyperpermeability for macromolecules. Structurally, an increased vascular density with focal areas of irregular capillary budding was found in the diabetic peritoneum. The hyperglycemia-induced structural and functional microvascular alterations were prevented by long-term treatment with neutralizing anti-VEGF monoclonal antibodies, whereas treatment with isotype-matched control antibodies had no effect. VEGF blockade did not influence microvascular density or macromolecular leakage in control rats, demonstrating specificity for the hyperglycemia-induced alterations. The present results thus support an causative link among high glucose exposure, upregulation of VEGF, and peritoneal microvascular dysfunction.

High Glucose Dialysis Solutions Increase Synthesis of Vascular Endothelial Growth Factors by Peritoneal Vascular Endothelial Cells

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 35-40 ◽  
Author(s):  
Moon Jeong Seo ◽  
Suk Joong Oh ◽  
Sung Il Kim ◽  
Kye Won Cho ◽  
Inho Jo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peritoneal Dialysis ◽  
High Glucose ◽  
Culture Supernatant ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Endothelial Growth Factors ◽  
Dialysis Solutions

♦ Objective Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). ♦ Methods The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. ♦ Results After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% ± 19%, p = 0.006) as compared with the control and mannitol (85% ± 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% ± 49%) than in the control and mannitol (94% ± 18%) groups. ♦ Conclusion High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.

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