Bozkurt Devrim, Cetin Pinar, Sipahi Savas, Hur Ender, Nar Hasim, Ertilav Muhittin, Sezak Murat, Duman Soner
Department of Nephrology, Ege University, Izmir, Turkey.
Perit Dial Int. 2008 Nov;28 Suppl 5:S38-42.
Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin-angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade.
To determine the advantages of RAS blockade in regression of EPS.
We divided 56 nonuremic albino Wistar rats into 6 groups: control group (n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group (n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group (n = 10), daily IP injection of CG (0 - 3 weeks) plus peritoneal rest (4 - 6 weeks). After 3 weeks of being injected with CG (0 - 3 weeks), a fourth group (n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group (n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group (n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 - 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined.
Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity (p < 0.05), and peritoneal thickness (p > 0.05). Dual blockade of RAS had no additional beneficial effects.
We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.
包裹性腹膜硬化症（EPS）是一种临床综合征，与肠梗阻症状以及脏层和壁层腹膜的不可逆硬化相关。腹膜透析（PD）患者很少发生EPS，这是一种发病机制不明的严重危及生命的疾病。已知血管紧张素II可促进各种组织中的纤维化和炎症。肾素-血管紧张素系统（RAS）阻断在高血压、慢性肾脏病和蛋白尿等疾病过程中具有优势。我们之前还表明，RAS阻断对高渗（3.86%）PD溶液诱导的腹膜改变具有有益作用。由于腹膜纤维化与其他纤维化过程具有相同特征，因此可能从RAS阻断中获益。
确定RAS阻断在EPS消退中的优势。
我们将56只非尿毒症白化Wistar大鼠分为6组：对照组（n = 10），每日腹腔内（IP）注射2 mL等渗盐水，共3周；CG组（n = 10），每日IP注射2 mL/200 g葡萄糖酸氯己定（CG），共3周；休息组（n = 10），每日IP注射CG（0 - 3周）加腹膜休息（4 - 6周）。在注射CG（0 - 3周）3周后，第四组（n = 9）用100 mg/L依那普利治疗（ENA组）；第五组（n = 10）用80 mg/L缬沙坦治疗（VAL组），第六组（n = 7）在饮用水中用100 mg/L依那普利 + 80 mg/L缬沙坦治疗（ENA+VAL组），持续另外3周（4 - 6周）。最后，用25 mL 3.86% PD溶液进行1小时的腹膜平衡试验。检测尿素的透析液与血浆比值（D/P尿素）、透析液白细胞计数、超滤量（UF）以及壁层腹膜的形态学变化。
暴露于CG 3周导致腹膜转运改变（D/P尿素增加，UF量减少；p < 0.05）和形态学改变（炎症、新生血管形成、纤维化和腹膜厚度增加；p < 0.05）。腹膜休息仅对超滤失败和透析液细胞计数有一些有益作用（p < 0.05）。然而，在超滤量、血管化（p < 0.05）和腹膜厚度方面（p > 0.05），RAS阻断比腹膜休息更有效。RAS的双重阻断没有额外的有益作用。
我们认为，在EPS的管理中，使用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂进行RAS阻断可能比休息是更有效的选择。
