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Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.

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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, α-smooth muscle actin (αSMA)] 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 (αSMA-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.

Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/PCr), the dialysate/initial dialysate ratio of glucose (D/Do) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (delta IPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTACCr, 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); delta IPV, 9.5 ml (-761 to 310); D/PCr, 0.76 (0.53 to 1.14); D/D0, 0.37 (0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and delta IPV. Systematic errors were found when D/PCr and MTACCr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.

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Dialysate fluids containing glucose polymers as osmotic agent are different from the conventional solutions, because they are iso-osmotic to plasma and produce transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the effects on fluid and solute kinetics, a comparison was made between a 7.5% glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based dialysate in 10 stable CAPD patients. In each patient three standard peritoneal permeability analyses (SPA) were done with the osmotic agents and concentrations mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased linearly in time in the icodextrin tests, whereas a hyperbola best described the glucose profiles. The effective lymphatic absorption rate with icodextrin was similar to the glucose based solutions. Mass transfer area coefficients of low molecular weight solutes with icodextrin were also similar to the values obtained with glucose, as was D/P creatinine. A positive correlation was present between the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which was absent in the glucose SPAs. This suggests that in patients with a larger effective peritoneal surface area, more ultrafiltration can be achieved by glucose polymer solutions. Clearances of beta 2-microglobulin (beta 2m) were higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P < 0.05). No differences were found for the larger serum proteins albumin, IgG and alpha 2-macroglobulin. Initial D/PNa-->was higher (0.96) with icodextrin than with the glucose based solutions (0.92), due to the higher Na+ concentration of icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of 1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86% glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration coefficient (UFC) of the total peritoneal membrane was assessed using 3.86% glucose (0.18 +/- 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed using icodextrin (0.06 +/- 0.008 ml/min/mm Hg). The difference between these represented the UFC through the transcellular pores, which averaged 50.5% of the total UFC, but with a very wide range (0 to 85%). An inverse relation existed between the duration of CAPD treatment and the total ultrafiltration coefficient (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the UFC of the small pores (r = -0.48, NS). The TCUFRo-60 min through the transcellular pores correlated with the sodium gradient, corrected for diffusion, in the first hour of the dwell (r = 0.69, P < 0.04), indicating that ...