Zhang Conghui, Bartosova Maria, Marinovic Iva, Schwab Constantin, Schaefer Betti, Vondrak Karel, Ariceta Gema, Zaloszyc Ariane, Ranchin Bruno, Taylan Christina, Büscher Rainer, Oh Jun, Mehrabi Arianeb, Schmitt Claus Peter
Center for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Nephrol Dial Transplant. 2023 Sep 29;38(10):2170-2181. doi: 10.1093/ndt/gfad031.
The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant.
Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry.
While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD.
Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.
腹膜透析(PD)液的非生理成分会导致进行性腹膜纤维化、血管增生和血管病变。关于肾移植(KTx)后这些改变的信息很少。
从81例5期慢性肾脏病(CKD5)儿科患者、72例使用低糖降解产物(GDP)腹膜透析液进行PD的儿童以及20例KTx后4 - 8周且在使用低GDP腹膜透析液之前的儿童获取壁层腹膜组织。通过数字组织形态计量学和定量免疫组织化学分析组织。
虽然慢性腹膜透析与腹膜血管增生有关,但肾移植后血管化程度与CKD5水平相当。与腹膜透析相比,间皮下CD45计数低40%,并且在多变量分析中与微血管密度独立相关。相比之下,肾移植后腹膜间皮剥脱、间皮下厚度和纤维蛋白丰度、活化的间皮下成纤维细胞数量以及间皮 - 间充质转化细胞数量相似。40%的移植患者存在弥漫性腹膜血小板内皮细胞黏附分子阳性。在年龄、腹膜透析病程、透析葡萄糖暴露和腹膜炎发生率相匹配的亚组中,肾移植后间皮下缺氧诱导因子1 - α丰度和血管生成素1/2比值较低,反映血管成熟,而小动脉和微血管p16和裂解的半胱天冬酶3较高。间皮下肥大细胞计数和白细胞介素 - 6较低,而与接受腹膜透析的儿童相比,转化生长因子 - β诱导的pSMAD2/3相似。
肾移植后,长期使用低GDP腹膜透析液引起的腹膜损伤较轻。虽然主要决定腹膜透析转运和超滤能力的腹膜微血管密度在肾移植后正常且腹膜炎症不那么明显,但弥漫性血小板内皮细胞黏附分子阳性和促纤维化活性普遍存在。