Mateijsen M A, van der Wal A C, Hendriks P M, Zweers M M, Mulder J, Struijk D G, Krediet R T
Department of Nephrology, Academic Medical Center Amsterdam, The Netherlands.
Perit Dial Int. 1999 Nov-Dec;19(6):517-25.
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.
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.
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).
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.
分析腹膜硬化（PS）患者腹膜的形态学变化。重点关注血管异常，因为持续接触基于葡萄糖的透析液可能导致糖尿病样改变，并且纵向转运研究提示腹膜血管表面积会增大。
在两项研究中对持续性非卧床腹膜透析（CAPD）患者的腹膜活检样本进行研究。排除糖尿病患者。在研究1中，将11份PS活检样本与三个CAPD治疗时长不同的对照组进行比较：0个月（n = 15）、2 - 25个月（n = 7）以及CAPD治疗时长> 25个月（n = 7）。第二项研究是一项病例对照研究，将长期对照组的6份活检样本与6份PS活检样本进行比较，两组在年龄和CAPD治疗时长上相匹配。所有活检样本均针对纤维化的存在及类型[苦味酸天狼星红、IV型胶原、α平滑肌肌动蛋白（αSMA）]以及新生血管形成（VIII因子）进行评分。通过计算机辅助平面测量法测量IV型胶原导致的血管壁增厚以及毛细血管扩张情况。
在研究1中，PS活检样本中的硬化性纤维化、间质IV型胶原沉积以及肌成纤维细胞（αSMA阳性细胞）数量均多于所有对照组的活检样本（p < 0.002）。此外，PS活检样本中每视野的血管数量更多（p < 0.01）。与所有对照组相比，PS活检样本中小动脉的血管壁增厚（p < 0.008）以及毛细血管扩张（p < 0.007）。第二项研究显示，PS活检样本与其对照组在硬化存在方面存在差异，但在纤维化程度上无差异。PS活检样本中每视野的血管数量高于对照组（p = 0.04）。同样，PS活检样本中血管壁增厚更为明显（p = 0.03）。PS活检样本中毛细血管扩张程度大于对照组（p = 0.07）。
腹膜纤维化可能先于腹膜硬化出现。间质层中IV型胶原的沉积以及肌成纤维细胞的存在可能是类似于糖尿病肾病瘢痕形成的病理过程的一部分。新生血管形成以及IV型胶原导致的血管壁增厚与葡萄糖诱导的微血管病变一致。这些异常以及毛细血管扩张可以解释长期CAPD患者中低分子量溶质的高透析液与血浆比率或质量转运面积系数。
