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M M Zweers

Publications and source records attributed to M M Zweers.

At least 19 recordsLinked to original sources
PubMed2001

Vascular endothelial growth factor in peritoneal dialysis: a longitudinal follow-up.

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations.

Amino Acids↗
PubMed2001

Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat.

BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions has been associated with diabetiform alterations of peritoneal tissue. A peritoneal infusion model in the rat was developed to study the effect of chronic infusion of a glucose-based dialysis solution and an isotonic non-glucose solution on the ultrastructure of the basement membranes of peritoneal capillaries. The effect of ageing was also studied in an untreated control group. METHODS: A vascular access port (Rat-o-Port) with attached peritoneal catheter was implanted subcutaneously in the neck of nine male Wistar rats. The rats were divided randomly into three groups: the glucose group (n = 3) was infused daily for 20 weeks with 60 ml/kg body weight 3.86% glucose solution. A control group (n = 2) was infused daily for 20 weeks with 60 ml/kg body weight Ringer's lactate. The untreated control group (n = 4) was studied at the onset of the experiment and after 20 weeks. Omental tissue was obtained from each rat at the end of the experimental period for ultrastructural examination. RESULTS: Extensive lamination of basement membranes of omental capillaries was found in the glucose group. This was in contrast to the untreated control group where clear, single basement membranes were seen at the onset of the experiment and after 20 weeks. These latter findings were similar to those in the Ringer's lactate group. CONCLUSIONS: The chronic infusion model in the rat is suitable for the investigation of the effects on the ultrastructure of peritoneal capillaries of chronic exposure to dialysis fluids. The duplications of basement membranes of omental capillaries found in the glucose group show a striking resemblance to those found in long-term peritoneal dialysis patients. This suggests a role for glucose in the development of peritoneal ultrastructural alterations found in long-term peritoneal dialysis.

Animals↗
PubMed2001

Nitric oxide-related experiments on peritoneal solute transport in the rabbit.

BACKGROUND: It is unclear whether nitric oxide (NO) is important in regulating peritoneal transport during non-infected peritoneal dialysis. METHODS: In 13 rabbits, 250 mg/l L-arginine, a substrate for NO synthesis, was added to a 3.86% glucose dialysis solution. N:(G)-monomethyl-L-arginine (L-NMMA) 25 mg/1, an inhibitor of NO synthase, was added to the dialysate in 10 rabbits. Standard peritoneal permeability analyses in rabbits were used to analyse the effects of these interventions on solute transport during 1-h dwells. The addition of 4.5 mg/l nitroprusside to the dialysate in five rabbits was used for validation of this model. RESULTS: Nitroprusside caused an 86% (48-233%) increase in albumin clearance, which is similar to the nitroprusside-induced increase found in humans (70%). Contrary to human studies, no effect was found on the mass transfer area coefficient (MTAC) of urea and creatinine, or on glucose absorption. L-Arginine did not affect either the MTAC of urea and creatinine, or the absorption of glucose. Peritoneal albumin clearance increased 18% (-24 to 609%). This resembles the NO-mediated effects of nitroprusside. Addition of L-NMMA caused no change in the solute transport rate. CONCLUSION: The rabbit dialysis model can be used for analysing the effects of interventions on peritoneal permeability characteristics, although the rabbit peritoneal membrane is probably less sensitive to NO compared with that of humans. L-Arginine-induced effects are similar to those of nitroprusside, which suggests that these effects possibly are mediated by NO. As L-NMMA did not affect peritoneal transport, it is unlikely that NO is involved in the regulation of peritoneal permeability in rabbits.

Animals↗
PubMed2001

Amphotericin B, mercury chloride and peritoneal transport in rabbits.

BACKGROUND: The effect of glucose-induced ultrafiltration in peritoneal dialysis is dependent on the presence and function of ultrasmall transendothelial cell water channels. The mercury-sensitive aquaporin-1 was thought to represent these transcellular pores. Amphotericin B (ampho B) has been reported to increase ultrafiltration in both experimental and patient studies. The objective of this study was to investigate the hypothesis that intraperitoneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit. MATERIAL AND METHODS: Eighteen female New Zealand White rabbits were included for peritoneal catheter implantation. Peritoneal transport parameters were determined in all rabbits by standard peritoneal permeability analysis (SPAR) with 3.86% glucose-based dialysis solution during a one-hour dwell prior the intervention SPARs, as a control. Ampho B (0.06 mg/kg body weight) was added to the dialysate for 3 (n = 9) or 5 consecutive days (n = 5) before investigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg body weight ampho B. In 3 rabbits 0.06 mg/kg body weight liposomal ampho B was administered i.p. during 3 days before intervention SPAR. Fifteen rabbits were investigated during a one-hour dwell with 0.1 mM HgCl2 containing 3.86% glucose-based dialysis solution, while they were anesthetized. Three of these underwent in vivo fixation with glutaraldehyde prior to the HgCl2 SPAR to prevent toxic effects of mercury on peritoneal tissues. RESULTS: Intraperitoneal administration of ampho B did enhance the change in intraperitoneal volume during a one-hour dwell after 3-day i.p. treatment with the low dose (p < 0.02), but it did not affect peritoneal solute permeability. This was likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged treatment or with the higher dose. Ultrafiltration decreased (8 ml/4 h to 1 ml/4 h, p < 0.03) after i.p. administration of HgCl2 with and without in vivo fixation, accompanied by a significant decrease in aquaporin-mediated water transport, estimated as the sieving of sodium (p < 0.001). Marked increases in the clearances of macromolecules were found after i.p. HgCl2 administration due to toxic effects: total protein clearance from 97 to 172 microl/min, p < 0.005, and albumin clearance from 59 to 158 microl/min, p < 0.005. These changes were less pronounced after in vivo fixation. CONCLUSION: Ampho B has likely no clinical relevance in treatment of ultrafiltration failure in PD patients. Aquaporin-mediated water transport could be inhibited and consequently ultrafiltration was reduced by i.p. administration of mercury chloride in our rabbit model.

Amphotericin B↗
PubMed2000

Neoangiogenesis in the peritoneal membrane.

OBJECTIVE: This study reviews relevant publications on the peritoneal vasculature and tries to establish morphological-functional relationships. DESIGN: The design is a review article. RESULTS: Recent morphological studies in peritoneal dialysis (PD) patients have shown the presence of diabetiform neoangiogenesis in long-term peritoneal dialysis. The same abnormalities could be induced in rats administered a high glucose dialysis solution daily for 20 weeks. The animals showed functional abnormalities in peritoneal transport similar to those found in long-term PD patients. Evidence was obtained in patients that vascular endothelial growth factor could be involved in glucose-induced peritoneal neoangiogenesis. CONCLUSIONS: Diabetiform peritoneal neoangiogenesis is an important pathogenetic factor in ultrafiltration failure in long-term peritoneal dialysis patients.

Animals↗
PubMed2000

Dialysate cancer antigen 125 levels in children treated with peritoneal dialysis.

Peritoneal mesothelial cells are important for local host defense and membrane integrity. Dialysate cancer antigen 125 (dCA125) has been shown to be a good marker for the mesothelial cell mass in adult peritoneal dialysis (PD) patients. In children on PD, no information is available yet. We measured dCA125 in 65 dialysate samples from 24 PD children with a median age of 9.2 years (range: 2-18 years) and a median treatment time of 2.6 years (range: 0.1-9.3 years) on PD. The median dCA125 concentration was 8 U/mL (range: 2.3-30.7 U/mL), and the CA125 appearance rate (CA125AR) was 66.5 U/min/1.73 m2 (range: 18-282 U/min/1.73 m2). On cross-sectional analysis, a negative correlation was found between dCA125 and duration of PD treatment (r = -0.3, p = 0.04). No relation was found between age and dCA125 or CA125AR when the first measurement from each child was considered. No correlation was found between dCA125 and the mass transfer area coefficient of creatinine (MTACcreat). Longitudinal analysis showed a negative trend in CA125AR with duration of PD treatment (p = 0.03). No relation was found between peritonitis incidence and dCA125 or CA125AR. In conclusion, no influence of age on dCA125 and CA125AR was found. Levels of dCA125 declined with the duration of PD treatment, reflecting mesothelial cell mass, but they did not correlate with the MTACcreat or the peritonitis incidence in stable PD children.

Adolescent↗
PubMed1999

Growth factors VEGF and TGF-beta1 in peritoneal dialysis.

The morphologic alterations in the kidney and the retina that can be present in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-beta (TGF-beta) is involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-beta1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions in relation to parameters of peritoneal transport. Standard peritoneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-beta1 in the circulation was bound to alpha2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-beta1 (P < .015) were significantly higher than expected when VEGF and TGF-beta1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta1 (LTGF-beta1). LVEGF correlated with the mass transfer area coefficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was also observed between the net ultrafiltration (622 mL/4 h, -43 to 938 mL/4 h) and LVEGF (r = -0.48) but did not reach significance. LVEGF and the duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-beta1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.

Biological Transport↗
PubMed1999

Substrate and inhibitor for nitric oxide synthase during peritoneal dialysis in rabbits.

OBJECTIVE: To investigate the possible influence of nitric oxide (NO) on peritoneal transport during non infected peritoneal dialysis. DESIGN: A chronic peritoneal dialysis model in New Zealand White rabbits (2624 g; range: 2251-3034 g) was used. In 13 rabbits, 250 mg/L L-arginine, a substrate for NO synthesis, was added to 3.86% glucose dialysate. N(G)-monomethyl-L-arginine (L-NMMA) 25 mg/L, an inhibitor of NO synthase, was added to the dialysate in 10 rabbits. Standard peritoneal permeability analyses in rabbits (SPAR) were performed to analyze the effects of these interventions on solute and fluid transport during 1-hour dwells. The addition of 4.5 mg/L nitroprusside to the dialysate in 5 separate experiments was used for validation of this model. MAIN OUTCOME: For the transport of urea and creatinine, mass transfer area coefficients (MTACs) were calculated. Furthermore, the glucose absorption, the peritoneal albumin clearance, peritoneal fluid kinetics, and the dialysate-to-plasma (D/P) ratio of nitrate were calculated. RESULTS: Nitroprusside caused an 86% (48%-233%) increase in albumin clearance, which is similar to the nitroprusside-induced increase found in humans. Contrary to the findings in human studies, no effect was found on the clearances of urea and creatinine, or on peritoneal fluid kinetics. This suggests a lower sensitivity of the rabbit peritoneal membrane for the effect of NO on small-solute transport. L-arginine affected neither the MTACs of urea and creatinine, nor the absorption of glucose. Also, peritoneal fluid kinetics were similar. Peritoneal albumin clearance increased 18% (-24%-609%). This result resembles the NO-mediated effects of nitroprusside. Addition of L-NMMA caused no change in the transport rate of small solutes, in albumin clearance, or in fluid profile. This result suggests that NO synthase is not induced during non infected peritoneal dialysis, which accords with previous studies. CONCLUSION: This rabbit dialysis model can be used for analyzing the effects of interventions on peritoneal permeability characteristics, although the rabbit peritoneal membrane is probably less sensitive to NO compared to that of humans. L-Arginine-induced effects are similar to those of nitroprusside, which suggests that these effects are possibly mediated by NO. Because L-NMMA did not affect peritoneal transport, it is unlikely that NO is involved in the regulation of peritoneal permeability during stable continuous ambulatory peritoneal dialysis.

Albumins↗
PubMed1999

Correction of sodium sieving for diffusion from the circulation.

Transcellular water transport (TCWT) can be estimated by Na- sieving. However, the assumption that the initial Na+ dialysate concentration (D0) is equal to the initial plasma concentration (P0) is not true for each patient. The difference leads to Na+ diffusion from the circulation to the dialysate, which diminishes the Na+ sieving. A model was developed to distinguish transcellular water transport from Na+ diffusion. We previously found evidence that the mass transfer area coefficient of urate (MTACurate) was similar to the MTACNa+. The MTAC is the product of the elimination constant (ke) and the volume of distribution (VD), the mean intraperitoneal volume. Because VD is known, the ke Na+ in each patient can be equated with the ke urate. The Na+ mass transfer from the circulation to the dialysate by diffusion can then be calculated for any time point during a dwell (Dt). Dt was subtracted from the measured Na+ dialysate concentration at 60 minutes. The corrected D/P Na+ then represents the actual Na+ sieving. Using 3.86% glucose dialysate, this approach was investigated in 15 stable peritoneal dialysis (PD) patients (normUF) and in 9 PD patients with low ultrafiltration (lowUF, < 400 mL/4 hours). The MTACurate was calculated according to Waniewski (W) and according to the Garred model (G). Similar calculations were also performed for the MTAC of creatinine (MTACcreat). Initial D/P Na+ was not different between the groups. When no diffusion correction was made, D/P60 Na+ in the lowUF group (median 0.898, range 0.870-0.949) was significantly higher (p < 0.025) than D/P60 Na+ in the normUF group (median 0.881, range 0.816-0.899). The difference disappeared after diffusion correction regardless of the correction model applied. However, at 240 minutes, D/P Na+ in the normUF group was significantly lower than in the lowUF group (median 0.880, range 0.839-0.952 vs median 0.942, range 0.866-0.987; p < 0.004). Even after correction, D/P Na+ in the normUF group was significantly lower: 0.847 normUF versus 0.893 lowUF (Wurate, p < 0.005); and 0.842 normUF versus 0.890 lowUF (Gcreat, p < 0.003). The correlation between the Wurate (the best theoretical diffusion correction) and Gcreat (the least) was: y = 0.99x + 0.0037. Furthermore, Bland and Altman analyses of Wurate and Gcreat at both 60 and 240 minutes resulted in random distribution around the means, with a slight overestimation in relation to the magnitude of Gcreat, as was expected. Gcreat can be used to make an accurate estimation of the contribution of Na+ diffusion in the time course of D/P Na+. It provides a simple way to more precisely determine Na+ sieving, and therefore TCWT. In conclusion, to avoid overestimation of impaired channel-mediated water transport, a Na+ diffusion correction should be made when D0 is not equal to P0 or in the case of a large vascular surface area.

Diffusion↗
PubMed1998

Effect of peritoneal dialysis fluid measured in vivo in a rat-model of continuous peritoneal dialysis.

To study the long-term effects of dialysis fluids on the peritoneal cavity, an in vivo model for continuous peritoneal dialysis in rats was developed. Mini vascular access ports were implanted subcutaneously in the neck of the rats and an attached catheter was instilled into the peritoneal cavity. Rats were injected daily with 10 mL of standard 3.86% Dianeal or saline for a period up to 12 weeks. In the peritoneal cavity an initial increase in total cells was observed after 4 weeks of fluid instillation. This had declined after 12 weeks. A similar trend was also seen for macrophage and neutrophil numbers, whereas the percentage of lymphocytes kept increasing in time. An effect of fluid instillation was observed on the density and the morphology of the mesothelial monolayer of the rats. A higher density of cells was observed after 12 weeks, and foci of young mesothelial cells within activated mesothelium were found. The results show that the rat model presented can be compared with the situation in the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients, and therefore is suitable for intervention studies.

Animals↗
PubMed1996

Demonstration of aquaporin-CHIP in peritoneal tissue of uremic and CAPD patients.

Aquaporin-CHIP is a 28 kD channel forming integral membrane protein. It acts as an osmotically driven, water-selective pore. The presence of aquaporin-CHIP has been demonstrated in the proximal tubule in the kidney and in the pleura, as well as in other tissues. During peritoneal dialysis a dissociation between the transport of water and sodium using hyperosmolar solutions has been reported, suggesting the presence of ultrasmall pores. Water channels, like aquaporin-CHIP, could be the morphological equivalent of these pores. We investigated the possible presence of aquaporin-CHIP in cryo-sections of peritoneal tissue using affinity purified human anti-CHIP IgC (P. Agre, Baltimore, MD). Peritoneal biopsies (omenta) were obtained at catheter insertion in 2 uremic patients with end-stage renal disease, and at catheter reimplantation of 1 patient treated with continuous ambulatory peritoneal dialysis (CAPD) for two years. Peritoneal tissue obtained at autopsy from 1 patient who had been on CAPD for four years, but in whom CAPD had been discontinued for five months, was also studied. Aquaporin-CHIP antiserum specific staining was found in the endothelial cells of the peritoneal capillaries in all patients. No obvious difference in the intensity of staining was seen between uremic and CAPD patients. This demonstration of aquaporin-CHIP in human peritoneal endothelial cells supports the hypothesis of the existence of ultrasmall pores within the peritoneal membrane. These water channels facilitate the transcellular transport of water, induced by an osmotic gradient, in the absence of sodium transport. It may be the explanation for the dissociation of water and sodium transport that occurs during hyperosmolar solutions. Aquaporin-CHIP is present in human peritoneal endothelial cells in both uremic and CAPD patients. Aquaporin-CHIP may be the morphological equivalent of the ultrasmall pores within the peritoneal membrane.

Aquaporin 1↗
PubMedDate not supplied

The standard peritoneal permeability analysis in the rabbit: a longitudinal model for peritoneal dialysis.

OBJECTIVE: The development of an experimental peritoneal dialysis (PD) model in rabbits to investigate peritoneal transport characteristics during a longitudinal follow-up and to assess normal values of these peritoneal transport parameters. DESIGN: Peritoneal transport parameters were determined in conscious, unrestrained rabbits by standard peritoneal permeability analysis adjusted for rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used. Dextran 70 (1g/L) was added to the dialysate to allow calculation of fluid kinetics. Dialysate samples were taken before, 10, and 40 minutes after instillation and at the end of the dwell. Blood was drawn at the end of the dwell. EXPERIMENTAL ANIMALS: Eighteen female New Zealand White rabbits (2565 g) were included for catheter implantation. SPARs were performed in 15 animals; the other 3 were excluded due to complications. MAIN OUTCOME: The mass transfer area coefficients (MTACs) of the low molecular weight solutes urea (MTAC(urea)) and creatinine (MTACcr) were calculated. The clearances of albumin (CIalb) and IgG (CI(IgG)), glucose absorption, and fluid transport were computed. Coefficients of intraindividual variation (Vc) were calculated for these parameters. RESULTS: The main complications were catheter obstruction and/or dislocation. Five rabbits underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable rabbits were performed and analyzed to obtain normal values. Means and standard deviations of the transport parameters were as follows: MTAC(urea) 2.24+/-0.57 mL/min, MTACcr 1.61+/-0.30 mU/min, CI(alb) 52.9+/-17.2 microL/min, CI(IgG) 44.5+/-22.9 UL/min. The transcapillary ultrafiltration rate was 0.66+/-0.13 mL/min and the lymphatic absorption rate 0.47+/-0.26 mL/min. The parameters of solute transport were upscaled to those in humans using two different methods. MTACs of low molecular weight solutes in rabbits and patients were of the same order of magnitude, but the clearance of albumin was approximately four times higher in rabbits than in patients, and that of IgG eight times. In all rabbits sieving of sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum at 40 min (p<0.003 vs the initial value), followed by a rise to 60 min. The minimal value was 0.884+/-0.002. The coefficients of variation calculated on 7 rabbits that underwent two or more SPARs were similar to those assessed from the patient data. This indicates stability of the model and reproducibility of the SPAR. CONCLUSION: The conscious rabbit model for PD can be used for repeated studies on peritoneal transport.

Absorption↗
PubMedDate not supplied

Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis.

OBJECTIVE: To analyze morphological changes in the peritoneum of peritoneal sclerosis (PS) patients. Emphasis was put on vascular abnormalities, because the continuous exposure to glucose-based dialysis solutions could cause diabetiform changes and because longitudinal transport studies suggested the development of a large peritoneal vascular surface area. DESIGN: Peritoneal biopsies from continuous ambulatory peritoneal dialysis (CAPD) patients were investigated in two studies. Diabetic patients were excluded. In study 1, 11 PS biopsies were compared to three control groups varying in duration of CAPD treatment: 0 months (n = 15), 2 - 25 months (n = 7), and > 25 months CAPD (n = 7). The second study was a case-control study, comparing six biopsies from the long-term control group to six PS biopsies, matched for age and duration of CAPD. All biopsies were scored for presence and type of fibrosis [Picro Sirius red, type IV collagen, alpha-smooth muscle actin (alphaSMA)] and for neoangiogenesis (factor VIII). Thickening of vascular walls by type IV collagen and vasodilation of capillaries were measured by computer-aided planimetry. RESULTS: In study 1 the presence of sclerosing fibrosis, deposition of interstitial type IV collagen, and the number of myofibroblasts (alphaSMA-positive cells) was greater in the PS biopsies than biopsies from all control groups (p < 0.002). Moreover, the number of vessels per field was higher in PS biopsies (p < 0.01). Vascular wall thickening of small arteries (p < 0.008) and vasodilation of capillaries were found in PS biopsies compared to all control groups (p < 0.007). The second study revealed differences in the presence of sclerosis but not in the extent of fibrosis between PS biopsies and their controls. The number of vessels per field in PS biopsies was higher compared to controls (p = 0.04). Also, thickening of the vascular wall was more marked in PS biopsies (p = 0.03). Vasodilation of capillaries was greater in PS biopsies than in controls (p = 0.07). CONCLUSION: Fibrosis of the peritoneum may precede peritoneal sclerosis. The deposition of type IV collagen and the presence of myofibroblasts in the interstitial layer could be part of a pathologic process similar to the scarring in diabetic nephropathy. Neoangiogenesis and thickening of the vascular wall by type IV collagen are consistent with glucose-induced microangiopathy.These abnormalities and the vasodilation of the capillaries can explain the high dialysate-to-plasma ratios or mass transfer area coefficients of low molecular weight solutes that can be found in long-term CAPD patients.

Actins↗
PubMedDate not supplied

Effect of fluid supplementation and modality on peritoneal permeability characteristics in a rat peritoneal dialysis model.

OBJECTIVE: Hemoconcentration may influence peritoneal permeability parameters in anesthetized animals without fluid supplementation. Therefore, the aim of this study was to investigate the effects of fluid supplementation on peritoneal permeability in an acute peritoneal dialysis model in anesthetized rats. DESIGN: To study the effect of fluid supplementation on peritoneal permeability characteristics, 24 anesthetized male Wistar rats were investigated in 3 groups during a 4-hour standardized peritoneal permeability analysis with a 3.86% glucose dialysis solution (SPARa). The groups included a control group with no fluid supplementation (None, n = 8), a group with continuous subcutaneous infusion of 0.9% NaCl 3 mL/hr (SC, n = 9), and a group with continuous intravenous infusion of 0.9% NaCl 3 mL/hr (IV, n = 7). Inflow, sampling, and outflow of the dialysate during the SPARa occurred via a cannula inserted intraperitoneally in the lower left quadrant of the abdomen. Blood was drawn at the end of the dwell. Baseline blood samples were obtained from six separate untreated rats. RESULTS: Plasma osmolality was significantly lower in the IV group (334+/-1.4 mOsm/kg) compared to the None group (348+/-0.7 mOsm/kg, p < 0.01), and not different from the SC group (335+/-6.4 mOsm/kg), but higher than baseline (314+/-5.3 mOsm/kg, p < 0.001). Urine production during the dwell was not different among the groups: None 10.6+/-5.3 mL; SC 8.0+/-6.0 mL; and IV 10.5+/-5.6 mL. Transcapillary ultrafiltration after 4 hours was significantly higher in the IV group (p < 0.05) compared to the other two groups. Net ultrafiltration and effective lymphatic absorption were similar in all groups. Mass transfer area coefficient of urea (MTACurea) was significantly greater in the IV group (155+/-23.2 microL/minute, p < 0.003), but not different between the None (118+/-16.2 microL/min) and SC (123+/-25.9 microL/min) groups. Correcting these for the baseline plasma concentration resulted in higher values, but the IV data remained greater than the SC and None groups (p < 0.01). The glucose absorption, albumin, and IgG clearances and the sieving of sodium were alike in all groups. CONCLUSION: It can be concluded that IV fluid supplementation is more effective in preventing dehydration than SC supplementation, and it enhanced some peritoneal permeability characteristics in anesthetized rats during a 4-hour investigation. It is therefore important to standardize fluid supplementation in experiments with anesthetized animals.

Animals↗
PubMedDate not supplied

Icodextrin degradation products in spent dialysate of CAPD patients and the rat, and its relation with dialysate osmolality.

OBJECTIVE: Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultrafiltration compared with glucose-based dialysis solutions. Colloid osmosis is the most likely mechanism, but studies in rats suggest it is caused by an increase in osmolality due to degradation of icodextrin. Therefore, human spent dialysate was analyzed with high-performance liquid chromatography (HPLC) using gel permeation size-exclusion chromatography. An increasing peak (with a low molecular weight, < 1000 Da) was observed during the dwell. The aim of this study was to quantitate breakdown products of icodextrin (which could explain this peak) and investigate whether there was a relationship with dialysate amylase concentration and dialysate osmolality. DESIGN: Long-dwell effluents (dwell time 9.15- 14.30 hours) obtained from 12 PD patients using a 7.5% icodextrin solution during the night were analyzed. The following icodextrin breakdown products were measured: maltotetraose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentaose (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a 6-hour dwell study. RESULTS: In the human studies, the median distribution of the sugars in the effluent was G4,6.7%; G3,16.5%; G2, 23.1%; and G1, 53.5%. The osmolality in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median contribution of the sugars G2 - G4 was 5.4 mOsm/kg H2O. No correlation was present between dialysate osmolality and duration of the dwell (r= -0.04, p= 0.91); nor was there a relation between the concentration of G2 and duration of the dwell (r = 0.50, p = 0.10). No relationship was found between the amount of amylase and the concentration of G2 in the effluent (r = 0.49, p = 0.10), nor between the total concentration of the sugars G2 - G4 in the spent dialysate and dialysate osmolality (r = -0.31, p = 0.33). However, a strong correlation was seen between urea concentration and osmolality (r= 0.85, p < 0.001), and also between sodium concentration and dialysate osmolality in the spent dialysate (r = 0.92, p < 0.0001). The levels of the sugars G2, G3, and G4 in effluent were higher than in unused dialysate, but lower than or similar to plasma levels. Concentrations of the sugars G5, G6, and G7 were lower in spent dialysate than in unused dialysate, and higher than in plasma. In the rat study, dialysate osmolality increased with the duration of the dwell. A clear relationship was present between osmolality and concentration of the sugars G2 - G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L. CONCLUSION: A 7.5% icodextrin-based dialysis solution used during the long exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependent mainly on concentrations of the small solutes urea and sodium in the effluent. The contribution of icodextrin degradation products was marginal. In the rat, however, a clear relationship was present between osmolality and icodextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the two species can be explained by the very high amylase concentrations in the rat, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.

Animals↗