NDT Advance Access originally published online on November 1, 2005
Nephrology Dialysis Transplantation 2006 21(1):208-216; doi:10.1093/ndt/gfi188
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Improved biocompatibility of bicarbonate/lactate-buffered PDF is not related to pH
1 Department of Molecular Cell Biology & Immunology, 2 Department of Nephrology and 3 Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands
Correspondence and offprint requests to: Mohammad Zareie, Department of Molecular Cell Biology & Immunology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Email: m.zareie{at}vumc.nl
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Abstract |
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Background. Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo.
Methods. Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n = 7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n = 8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n = 5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n = 7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n = 8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed.
Results. Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters P<0.05), accompanied by increased glucose absorption and reduced ultrafiltration capacity. Daily exposure to standard or acidified bicarbonate/lactate-buffered PDF improved the performance of the peritoneal membrane, evidenced by reduced new vessel formation in omentum (P<0.02) and parietal peritoneum (P<0.008), reduced fibrosis (P<0.02) and improved ultrafiltration capacity. No significant differences were found between standard and acidified bicarbonate/lactate-buffered PDF. During PET, acidic PDF was neutralized within 15 to 20 min.
Conclusion. The bicarbonate/lactate-buffered PDF, acidity per se did not contribute substantially to peritoneal worsening in our in vivo model for PD, which might be explained by the buffering capacity of the peritoneum.
Keywords: Peritoneal dialysis; acidity; angiogenesis; fibrosis; rats
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Introduction |
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Long-term exposure to conventional glucose-based peritoneal dialysis fluid (PDF) leads to functional and structural alterations of the peritoneal membrane [1,2].
Human biopsy studies and animal experiments have identified an increase in PDF-induced vasculature of the peritoneal membrane and progressive peritoneal fibrosis [2–4]. Furthermore, the integrity of the mesothelial cell layer was affected during PD [3,4]. These changes are thought to be instrumental in the progressive worsening of the peritoneal membrane.
The bioincompatibility of conventional heat-sterilized PDF might be attributed either to the low pH, the lactate buffer, hypertonicity, the high concentration of glucose, glucose degradation products (GDPs) or a combination of these factors. It has been shown that a high concentration of glucose, used as osmotic agent, is cytotoxic to peritoneal cells [5]. In this respect, we [4] and others [6] have reported a major contribution of glucose to the induction of angiogenesis and fibrosis in experimental PD models. The process of heat sterilization of glucose-based PD fluids leads to the formation of GDPs [7]. Several in vitro studies have suggested that the presence of several aldehydes and 1,2-dicarbonyl compounds is partly responsible for the cytotoxicity of these fluids [8,9]; however, we have previously demonstrated a minor effect of GDPs on morphological/cellular alterations of the peritoneum in vivo [4]. GDPs can also promote the irreversible formation of advanced glycation end products (AGEs), which in turn can potentially contribute to the toxicity of PD fluids [10]. There is considerable evidence suggesting cytotoxic effects of lactate as the common buffer used in the conventional PD fluids [11]. Indeed, our earlier work showed that daily instillation of acidic lactate buffer, without glucose, resulted in mild morphological/cellular changes in vivo [4], indicating the contribution of lactate, in combination with low pH, to the peritoneal injury in vivo. Apart from these fluid constituents, a low pH per se might harm the peritoneal membrane.
In order to determine the chronic effects of low pH per se on various functional and morphological parameters in a rat model of PD, we have compared the chronic effects of a conventional lactate-buffered PDF (pH 5.2) with standard bicarbonate/lactate-buffered PDF (pH 7.4) and an acidified bicarbonate/lactate-buffered PDF (pH 5.2). Results did not support a major role for PDF acidity per se in the induction of peritoneal alterations in vivo.
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Materials and methods |
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Animals
Throughout the study, we used male Wistar rats (Harlan CPB, Horst, The Netherlands), weighing 180–200 g at the start of the experiment. The rats were acclimatized for 1 week before any treatment. Animals were maintained under conventional laboratory conditions and were given free access to water and food. The experiment was reviewed and approved by the local ethical committee on the use of laboratory animals.
Experimental design
Animals were daily exposed to 10 ml of different solutions (Table 1) via a peritoneal catheter connected to a subcutaneous mini vascular access port [3,4]. The first group (n = 7) received conventional lactate-buffered glucose containing PDF (Dianeal® PD4, 3.86% glucose, pH 5.2, high GDP content, Baxter R&D, Utrecht, the Netherlands). The second group (n = 8) received standard bicarbonate/lactate-buffered glucose containing PDF (Physioneal ®, 3.86% glucose, pH 7.4, low GDP content, Baxter R&D, Utrecht, the Netherlands). The third group received the same bicarbonate/lactate-buffered PDF as the second group, but was adjusted to pH 5.2 by adding 1 N hydrochloride (acidified bicarbonate/lactate-buffered PDF, n = 5). At room temperature, the pH of this fluid remained stable for at least 20 h, while at 37°C the pH value was slightly elevated from 5.2 to 5.7. The buffer group (n = 7) received bicarbonate/lactate buffer, without glucose, with physiological pH. Control animals with or without peritoneal catheters served as control groups (n = 8/group). After 8 weeks of fluid instillation, animals were weighted and no significant differences were found in the body weight. Furthermore, no apparent clinical abnormalities were observed. Thereafter, peritoneal membrane function was assessed by performing a 2 h peritoneal equilibration test (PET), using 30 ml of conventional 3.86% glucose containing PDF. During PET, samples of 0.5 ml were collected for pH measurements after 15 and 20 min. Total number of peritoneal cells in the PET effluents and their cellular compositions were determined, as previously described [3]. Hyaluronan (HA) concentrations were measured in the cell-free PET dialysates by ELISA, with a detection level of 50 ng/ml [4]. Glucose levels were determined in the dialysate effluents by the hexokinase method on a Roche/Hitachi Modular P800, and the percentage of glucose absorption was calculated as [1 – (final dialysate glucose concentration) x(drained volume)/200 mM x 30 ml] x 100. After PET, peritoneal tissues were collected for morphometric analysis. To exclude peritonitis, peritoneal cell-free PET fluids were checked for the presence of bacteria, which were not found. Omental and mesenteric tissues were also inspected for the presence of adherent bacteria and/or neutrophils, and no bacteria or an abnormal number of neutrophils were found.
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Cellular/morphometric analysis
Omentum
The number of blood vessels was quantified in stretched preparations of the omentum (two sections of approximately 4 cm2/rat) after staining with toluidine blue, as previously described [3,4]. Since omental milky spots (local aggregates of immune cells) are the major route through which leukocytes migrate into the peritoneal cavity and because their size and number reflect the activated state of the peritoneum, we determined their number and size by light microscopy, as previously described [3,4]. Total milky spot surface area was calculated by multiplying both parameters.
Parietal peritoneum
Cryostat sections of large specimens of the parietal peritoneum (two samples of approximately 10 cm2) were cut (8 µm), embedded and stained in a standardized fashion. The thickness of the submesothelial extracellular matrix (ECM) was determined after Van Gieson staining (Merck KGaA, Darmstadt, Germany), and the average of 10 independent measurements was calculated for each section and expressed in microns [3,4]. The number of submesothelial blood vessels was quantified, using anti-CD31 (PECAM; Serotec, Oxford, UK) and expressed as the number of vessels per millimeter length of the mesothelial cell layer [4].
Liver
Mesothelial liver imprints were dried and stained by May-Grünwald/Giemsa, as described before [3,4]. The number of cells per 0.1 mm2 area was counted, and the average number of cells in 16 areas was calculated for each slide and expressed as cells per square millimetre.
Electron microscopy
Portions of the dissected omental tissue of at least 3 animals/group were prepared for electron microscopy according to standard procedures [3,4].
Statistical analysis
Data in the table are expressed as medians and 25th to 75th interquartile ranges. Results in graphs are expressed as medians and 25th to 75th interquartile ranges with the spread from 10th to 90th percentile. Data were analysed statistically using the non-parametric Mann–Whitney U-test. A value of P<0.05 was regarded as significant.
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Results |
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Conventional PDF induced severe peritoneal alterations
Generally, long-term exposure to conventional PDF evoked a chronic sterile inflammatory response in the peritoneum characterized by tissue remodelling processes such as angiogenesis and fibrosis, as well as a serosal wound healing reaction of the mesothelium manifested as a strong mesothelial regenerative response and the production of HA. The PDF-induced morphological/cellular alteration of the peritoneum was accompanied by functional alterations. The present data are in good agreement with previous reports [3,4]. Specifically, rats exposed to the conventional PDF showed an increased glucose absorption, accompanied by loss of ultrafiltration capacity, compared with both control groups and animals treated with bicarbonate/lactate buffer (Figure 1). Conventional PDF induced a significant angiogenesis in the omentum (Figures 2 and 3) and parietal peritoneum (Figures 2 and 4), when compared with both controls and the buffer group. The submesothelial ECM of the parietal peritoneum was significantly thickened in the conventional PDF group (Figure 5) compared with control rats with or without catheters and rats exposed to the buffer solution. In addition, the conventional PDF evoked a significant milky spot response in the omentum compared with both control groups (Table 2). Since the mesothelium is the first cell layer that comes in contact with the fluid, the condition of this cell layer was carefully inspected by light and electron microscopy. Light microscopic observation revealed a significant difference in the mesothelial cell density on the liver between the conventional PDF and both control groups (Table 2), with no significant difference between the conventional PDF and the buffer group (P = 0.80). Furthermore, using electron microscopy, we observed focal damage to the mesothelial cell layer after exposure to the conventional PDF, along with adhesion of macrophages, while the mesothelium was intact in both control groups and after infusion of bicarbonate/lactate buffer (data not shown). Since the production of HA by injured mesothelial cells reflects a wound healing response [12], along with a strong mesothelial regenerative reaction, we have measured the amount of HA in the PET effluents (Table 2). A significantly higher level of HA was found in rats exposed to the conventional PDF compared with both control groups and this was near significance compared with the buffer group (P = 0.07). The analysis of PET dialysates furthermore revealed a significant cell influx towards the peritoneal cavity in the conventional PDF group, compared with both control groups (Table 2), but not compared with the buffer group (P = 0.95). No significant differences were found in the percentage of macrophages or lymphocytes; however, the percentage of neutrophils was higher in the conventional (P<0.003) compared with untreated control animals. By contrast, the percentage of eosinophils and mast cells was higher in control animals with or without catheters, compared with the buffer and the conventional PDF group.
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Standard bicarbonate/lactate-buffered PDF better preserved the peritoneum
Compared with the conventional PDF, daily exposure to standard bicarbonate/lactate-buffered PDF resulted in a non-significant tendency towards a better ultrafiltration capacity and reduced glucose absorption (Figure 1). Rats exposed to standard bicarbonate/lactate-buffered PDF showed a lower number of newly formed blood vessels in the omentum (Figure 2A) or in the parietal peritoneum (Figure 2B), compared with the conventional PDF group. Compared with the conventional PDF group, fibrosis was developed less profoundly in rats treated with standard bicarbonate/lactate-buffered PDF (Figure 5). Standard bicarbonate/lactate-buffered PDF evoked a weaker milky spot response in the omentum, than the conventional PDF group (P = 0.05; Table 2). No significant difference was found in the number of mesothelial cells on liver or the amount of HA (P = 0.62) between rats instilled with standard bicarbonate/lactate-buffered PDF and rats exposed to the conventional PDF (P = 0.73). Electron microscopic inspection of the mesothelium revealed a slightly better condition of this cell layer in rats exposed to the standard bicarbonate/lactate buffered PDF, compared with animals treated with the conventional PDF (results not shown). The total number of recruited cells in the standard bicarbonate/lactate-buffered PDF group (P = 0.40) and their composition did not significantly differ from those observed in the conventional PDF (Table 2).
No major contribution of low pH to bicarbonate/lactate-buffered PDF-induced peritoneal alterations
In order to investigate whether the observed differences between the conventional and standard bicarbonate/lactate-buffered PDF can be explained by the effect of acidity per se, we have first tried to neutralize the conventional PDF. However, we did not succeed in raising the pH of the conventional PDF to 7.4 without using bicarbonate, which obviously alters the buffering system. Neutralizing of conventional PDF by NaOH was not stable, as the pH declined rapidly. On the contrary, we stably acidified the standard bicarbonate/lactate-buffered PDF with NaOH (pH adjusted to 5.2) and compared that with the standard bicarbonate/lactate-buffered PDF. We found no significant differences in glucose absorption (P = 0.11) or ultrafiltration volume (P = 0.57) between animals treated with acidified and standard bicarbonate/lactate-buffered PDF. Likewise, no significant differences were found in the number of newly formed blood vessels between standard and acidified bicarbonate/lactate-buffered solutions (P = 0.08 and P = 0.10 in omentum and parietal peritoneum, respectively), although a mild reduction in vessel density might be suggested in the acidified bicarbonate/lactate-buffered PDF. The extent of fibrosis in the parietal peritoneum (P = 0.45) and the milky spot reaction in the omentum (P = 0.75) was similar between animals exposed to acidified and standard bicarbonate/lactate-buffered PDF. Since the acidity might greatly affect the mesothelium, the condition of the mesothelial cell layer and their density on the liver as well as the amount of HA production (mainly by mesothelial cells) in the acidified bicarbonate/lactate-buffered PDF was carefully compared with those in the standard bicarbonate/lactate-buffered PDF. No significant differences were found in the mesothelial regenerative response on liver (P = 0.41). Although the median of HA concentration was higher in the acidified bicarbonate/lactate-buffered PDF, no significant difference was found in the HA concentration between both solutions (P = 0.34; Table 2). Using electron microscopy, the mesothelium was found to be similarly damaged focally in both groups. Although the total number of peritoneal cells was slightly, but not significantly, higher in the acidified bicarbonate/lactate-buffered PDF group (P = 0.08), no significant differences were found in the cellular composition of PET dialysates between the standard and acidified bicarbonate/lactate-buffered PDF group (Table 2). Taken together, we found that acidity per se had a minor, if any, effect on the function or morphology of the peritoneum in vivo.
Conventional PDF induced more profound peritoneal changes than acidified bicarbonate/lactate-buffered PDF
While the percentage of glucose absorption was similar between the conventional PDF and acidified bicarbonate/lactate-buffered PDF groups (P = 0.84), the ultrafiltration capacity was significantly reduced in rats exposed to the conventional PDF compared with animals treated with acidified bicarbonate/lactate-buffered PDF (P<0.02). Animals exposed to the conventional PDF showed a more severe angiogenesis in the omentum (P<0.005) and in the parietal peritoneum (P<0.002) compared with rats instilled with acidified bicarbonate/lactate-buffered PDF. The thickness of submesothelial ECM increased almost significantly in the conventional PDF group compared with acidified bicarbonate/lactate-buffered PDF (P = 0.07). Furthermore, we found no significant differences between these two solutions with respect to the omental milky spot response (P = 0.14), mesothelial cell density on liver (P = 0.73) or the amount of HA (P = 0.53). The mesothelium was more profoundly damaged in the conventional PDF group compared with the acidified bicarbonate/lactate-buffered PDF (data not shown). The total number of recruited cells was higher in the acidified bicarbonate/lactate-buffered PDF group compared with the conventional PDF group (P<0.003), with no other differences in the cellular composition (Table 2). Thus, despite identical pH and similar glucose concentrations, acidified bicarbonate/lactate-buffered PDF was found to be more biocompatible.
Buffering capacity of the peritoneal membrane
During 2 h dwell, which was performed with conventional lactate-buffered PDF (3.86% glucose, pH 5.2), samples were taken for pH measurements. Fifteen minutes after initiating PET, the mean pH value of dialysate sample was 
6.8 in the untreated, the catheter and the buffer group, while it was 7.0 or more in the three other groups (Table 3). The same results were found after 20 min, as the pH increased to 6.9–7.0 in the untreated, catheter or the buffer groups, while it was 7.2–7.3 in all other groups. Thus, the low pH of the lactate-buffered PDF was faster corrected in all groups that were chronically exposed to glucose-containing PDF.
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Discussion |
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We investigated the possible pathological effects of PDF acidity per se on the function and morphology of the peritoneum. Using a number of morphometric and functional parameters, we could not show any significant contribution of low pH to the bicarbonate/lactate-buffered PDF-induced alterations in vivo. This conclusion should be interpreted with caution as it is based on a limited number of experimental parameters and animals in a pre-clinical model.
The data presented in this report are in good agreement with previous studies showing a better preservation of the peritoneal function and morphology after exposure to standard bicarbonate/lactate buffer, compared with the conventional PDF [3,13]. Since these two solutions differ in not only their pH but also in the amount of GDPs and the buffering system, the observed bioincompatible effects of the conventional PDF could potentially be caused by low pH, GDPs, lactate buffer or a combination of these factors. In order to determine the sole effect of GDPs on the morphology of the peritoneum in vivo, we have previously compared a heat-sterilized with a filter-sterilized lactate-buffered PDF [4]. Interestingly, we could not show any major impact of GDPs with respect to angiogenesis and fibrosis. However, a limitation of that study was that the in vivo effect of GDPs was investigated under low pH/lactate conditions, which might overshadow eventual GDP effects. In the same study, we have found that the instillation of acidic lactate buffer could induce changes in the peritoneum, however, we could not separate the effects of the lactate buffer and low pH in that study. In this respect, several studies in the PD field made efforts to determine the effect of low pH, however these studies were either performed in vitro [14], or were acute experiments [15]. Some other studies with chronic animal models focused on transport parameters but provided no morphometeric data [16,17]. In contrast to these studies, the design of the present work allowed us to determine the chronic, in vivo effects of low pH per se (separate from lactate buffer) on not only the function but also the morphology of the peritoneum. Importantly, we found no clear contribution of acidity to PD-induced morphological and functional changes, although a tendency towards stepwise worsening was observed between the conventional, acidified bicarbonate/lactate-buffered and physiological bicarbonate/lactate-buffered PDF in some of the parameters (glucose absorption, omental milky spot response and peritoneal fibrosis). The only almost significant difference between physiological and acidified bicarbonate/lactate-buffered PDF was the number of recruited cells toward peritoneal cavity during PET procedure, which is an important parameter of host defence mechanism. Owing to the lack of other host defence data, we cannot exclude the possible effect(s) of low pH on defence parameters. Lack of acidic pH effect might be explained by the results obtained by the present study and by others [17] that an acidic solution is rapidly neutralized after instillation. We observed that 30 ml of an acidic solution was pH corrected within 15–20 min; however, in this study, all rats were treated daily with only 10 ml of different PDF, which would theoretically be neutralized even faster. We speculate that the pH neutralizing capacity of the peritoneum is related to the surfactant layer on the mesothelium [18]. In addition, although our preliminary data indicate that 10 ml PDF would be absorbed within 16 h in our model, we cannot exclude the possibility that the faster neutralizing ability of the peritoneum in animals treated with glucose-containing PDF might be due to a rest volume from the previous day. Hence, our data clearly demonstrates the superior buffering capacity of the peritoneum in vivo in comparison with cell culturing systems, which might explain more profound effects of acidity in in vitro experiments [15].
Interestingly, we found some clear differences between conventional PDF and acidified bicarbonate/lactate-buffered PDF with respect to the function and morphology of the peritoneum. These two solutions differ in the amount of GDPs and their buffering system. The observed differences between these solutions might be explained by differences in the buffering system, because we could not find any major effects of GDPs on the morphology of the peritoneum under low pH/lactate condition [4], although this might be different under neutral bicarbonate/lactate condition. In vitro, the addition of sodium lactate, either alone or in the presence of D-glucose, was found to enhance TGF-beta 1 and MCP-1 secretion by human peritoneal mesothelial cells [19]. The conventional PDF contains 40 mM/l lactate, while the standard bicarbonate/lactate-buffered PDF contains 15 mM/l lactate and 25 mM/l bicarbonate. Thus, the beneficial effects of acidified bicarbonate/lactate-buffered PDF over the conventional PDF can be explained by the lower concentration of lactate in the acidic bicarbonate/lactate-buffered PDF. The instrumental role of the buffering system in the PDF bioincompatibility can also be observed by comparing the effect of lactate and bicarbonate/lactate buffer on the formation of new blood vessels in the peritoneum. Compared with the conventional PDF, the acidic lactate buffer in our previous study [4] induced 30% less angiogenesis in omentum, whereas bicarbonate/lactate buffer induced 73% less angiogenesis in the present study. In the parietal peritoneum, 69% and 91% less angiogenesis was observed by lactate and bicarbonate/lactate buffer, respectively. Thus, the bioincompatibility of the conventional PDF might be partially related to the lactate buffering system. A recent study has suggested a synergistic cytotoxicity of GDPs and acidity on cultured mesothelial cells under the existence of lactate [20]. The design of our study did not allow us to investigate any synergistic effects of either GDPs and lactate or lactate and acidity because both the acidified and standard bicarbonate/lactate-buffered PDF contain a low amount of GDPs and lactate. However, the fact that we previously found no difference in the degree of fibrosis, the extent of angiogenesis or the condition of the mesothelium between heat- (GDP-rich) and filter-sterilized (no GDPs) conventional PDF [4] exclude the possible synergistic effect of GDPs with either lactate or low pH in the presence of glucose in our model.
In addition to clarifying the contribution of low pH, our experimental set up provided information about the effect of glucose (in combination with hyperosmolarity) on peritoneal injury during PD. The number of newly formed blood vessels in both the parietal and visceral peritoneum tended to be higher in animals exposed to the standard bicarbonate/lactate-buffered PDF compared with the buffer. In addition, significantly more fibrosis was developed in the standard bicarbonate/lactate-buffered PDF group compared with the buffer group. These results are in good agreement with our previous report [4] and extend our understanding about the contribution of glucose to the peritoneal injury in vivo.
We thus conclude that in the bicarbonate/lactate buffered PDF, acidity per se did not contribute substantially to peritoneal worsening in our in vivo model for PD, which might be explained by the buffering capacity of the peritoneum.
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Acknowledgments |
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This study was financially supported by Baxter Health Care, Europe.
Conflict of interest statement. None declared.
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References |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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- Davies SJ, Phillips L, Naish PF, Russell GI. Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis. J Am Soc Nephrol 2001; 12: 1046–1051
[Abstract/Free Full Text] - Williams JD, Craig KJ, Topley N et al. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol 2002; 13: 470–479
[Abstract/Free Full Text] - Hekking LHP, Zareie M, Driesprong BA et al. Better preservation of peritoneal morphologic features and defense in rats after long-term exposure to a bicarbonate/lactate-buffered solution. J Am Soc Nephrol 2001; 12: 2775–2786
[Abstract/Free Full Text] - Zareie M, Hekking LHP, Welten AGA et al. Contribution of lactate buffer, glucose and glucose degradation end products to peritoneal injury in vivo. Nephrol Dial Transplant 2003; 18: 2629–2637
[Abstract/Free Full Text] - Ito T, Yorioka N, Yamamoto M, Kataoka K, Yamakido M. Effect of glucose on intercellular junctions of cultured human peritoneal mesothelial cells. J Am Soc Nephrol 2000; 11: 1969–1979
[Abstract/Free Full Text] - Stoenoiu MS, De Vriese AS, Brouet A et al. Experimental diabetes induces functional and structural changes in the peritoneum. Kidney Int 2002; 62: 668–678[CrossRef][Web of Science][Medline]
- Schalkwijk CG, Posthuma N, ten Brink HJ et al. Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids. Perit Dial Int 1999; 19: 325–333
[Abstract/Free Full Text] - Linden T, Cohen A, Deppisch R et al. 3,4-Dideoxyglucosone-3-ene(3,4-DGE): a cytotoxic glucose degradation product in fluids for peritoneal dialysis. Kidney Int 2002; 62: 697–703[CrossRef][Medline]
- Amore A, Cappelli G, Cirina P et al. Glucose degradation products increase apoptosis of human mesothelial cells. Nephrol Dial Transplant 2003; 18: 677–688
[Abstract/Free Full Text] - Miyata T, Horie K, Ueda Y et al. Advanced glycation and lipidoxidation of the peritoneal membrane: respective roles of serum and peritoneal fluid reactive carbonyl compounds. Kidney Int 2000; 58: 425–435[CrossRef][Web of Science][Medline]
- Jorres A, Bender TO, Finn A et al. Biocompatibility and buffers: effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function. Kidney Int 1998; 54: 2184–2193[CrossRef][Medline]
- Yung S, Thomas GJ, Davies M. Induction of hyaluronan metabolism after mechanical injury of human peritoneal mesothelial cells in vitro. Kidney Int 2000; 58: 1953–1962[CrossRef][Medline]
- Mortier S, Faict D, Schalkwijk CG, Lameire NH, De Vriese AS. Long-term exposure to new peritoneal dialysis solutions: effects on the peritoneal membrane. Kidney Int 2004; 66: 1257–1265[CrossRef][Web of Science][Medline]
- Ha H, Yu MR, Choi HN et al. Effects of conventional and new peritoneal dialysis solutions on human peritoneal mesothelial cell viability and proliferation. Perit Dial Int 2000; 20 [Suppl 5]: S10–S18
- Mortier S, De Vriese AS, Van de Voorde J, Schaub TP, Passlick-Deetjen J, Lameire NH. Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role of acidity, buffer choice, glucose concentration, and glucose degradation products. J Am Soc Nephrol 2002; 13: 480–489
[Abstract/Free Full Text] - Park MS, Heimburger O, Waniewski J et al. The effect of dialysate acidity on peritoneal solute transport in the rat. Perit Dial Int 1995; 15: 312–319[Abstract]
- Musi B, Carlsson O, Rippe A, Wieslander A, Rippe B. Effects of acidity, glucose degradation products, and dialysis fluid buffer choice on peritoneal solute and fluid transport in rats. Perit Dial Int 1998; 18: 303–310
[Abstract/Free Full Text] - Hills BA. Role of surfactant in peritoneal dialysis. Perit Dial Int 2000; 20: 503–515
[Abstract/Free Full Text] - Wong TY, Phillips AO, Witowski J, Topley N. Glucose-mediated induction of TGF-beta 1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent. Kidney Int 2003; 63: 1404–1416[CrossRef][Web of Science][Medline]
- Tomo T, Okabe E, Yamamoto T et al. Synergistic cytotoxicity of acidity and 3,4-dideoxyglucosone-3-ene under the existence of lactate in peritoneal dialysis fluid. Ther Apher Dial 2005; 9: 182–187[Medline]
Accepted in revised form: 9. 9.05
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