Vascular and Interstitial Changes in the Peritoneum of Capd Patients with Peritoneal Sclerosis

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Abstract

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.

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Most cited references 41

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Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.

L P Aiello, R L Avery, P Arrigg … (1994)

Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

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Record: found
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Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis.

Alan J Bryan, David Russell, Andrew Phillips … (1996)

Peritoneal infection and poor ultrafiltration continue to be the major causes of treatment failure in CAPD. The combined effects of peritonitis and the continuous exposure to dialysis fluid remain the most likely candidates affecting the peritoneum in the long term. The purpose of this study was to observe the effects of peritonitis and dialysis on longitudinal peritoneal function. The peritoneal equilibration test (PET) was utilized to quantify longitudinal changes in low-molecular-weight solute transfer (D/P(creat)) and ultrafiltration (UF) in 233 patients treated with CAPD. Of these, 166 represented an unselected cohort (Group 1) studied prospectively from commencing treatment for up to 54 months, and 67 were selected patients (Group 2) with PET data available at commencement of the study, having been on dialysis for a minimum of 18 months. PETs were performed either 6-monthly or following peritonitis episodes. Data on the short-term effect of peritonitis kinetics were pooled for groups 1 and 2. Single, isolated episodes (n = 86) had no significant effect on D/P(creat) or UF, whereas recurrences or clusters of infection (n = 70) caused increases in D/P(creat) and reductions in UF, the significance of which increased with the number of episodes. There were significant correlations between both changes in D/P(creat) and UF with the cumulative dialysate leukocyte count, regardless of infecting organism, suggesting that intensity of peritoneal inflammation is also important. Those organisms associated with greater change in peritoneal kinetics, e.g. S. aureus, Pseudomonas, also had the highest neutrophil counts. The longitudinal changes in peritoneal kinetics were analysed for patients in group 1 only. There was a highly significant increase in D/P(creat) after 6 months treatment; this increased further with time on treatment, reaching further significance at 42 and 48 months. There was an associated reduction in UF. In view of the short-term effects of peritonitis on kinetics group 1 was further subdivided into patients who were either peritonitis free or only experienced isolated infections, group 1a, and those that had multiple infection episodes, group 1b. Treatment drop-out, due to death or technical failure occurred at double the rate in group 1b, who also had significantly higher D/P(creat) and lower UF at 1, 6, 12, 18 and 24 months of treatment. Group 1a subsequently caught up, however, indicating that peritonitis is not the only factor influencing long-term changes in peritoneal kinetics. These data suggest that solute transfer increases and UF declines with time on peritoneal dialysis. This process is exacerbated and accelerated by peritonitis, and appears to be proportional to the degree of associated inflammation and number of infections in close proximity.