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

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, 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.