Bartosova Maria, Schaefer Betti, Vondrak Karel, Sallay Peter, Taylan Christina, Cerkauskiene Rimante, Dzierzega Maria, Milosevski-Lomic Gordana, Büscher Rainer, Zaloszyc Ariane, Romero Philipp, Lasitschka Felix, Warady Bradley A, Schaefer Franz, Ujszaszi Akos, Schmitt Claus Peter
Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Department of Pediatrics, Motol University Hospital, Prague, Czechia.
Front Physiol. 2019 Apr 2;10:356. doi: 10.3389/fphys.2019.00356. eCollection 2019.
The impact of peritoneal dialysis (PD) associated peritonitis on peritoneal membrane integrity is incompletely understood. Children are particularly suited to address this question, since they are largely devoid of preexisting tissue damage and life-style related alterations. Within the International Peritoneal Biobank, 85 standardized parietal peritoneal tissue samples were obtained from 82 children on neutral pH PD fluids with low glucose degradation product (GDP) content. 37 patients had a history of peritonitis and 16 of the 37 had two or more episodes. Time interval between tissue sampling and the last peritonitis episode was 9 (4, 36) weeks. Tissue specimen underwent digital imaging and molecular analyses. Patients with and without peritonitis were on PD for 21.0 (12.0, 36.0) and 12.8 (7.3, 27.0) months ( = 0.053), respectively. They did not differ in anthropometric or histomorphometric parameters [mesothelial coverage, submesothelial fibrosis, blood, and lymphatic vascularization, leukocyte, macrophage and activated fibroblast counts, epithelial-mesenchymal transition (EMT), podoplanin positivity and vasculopathy]. VEGF and TGF-ß induced pSMAD abundance were similar. Similar findings were also obtained after matching for age and PD vintage and a subgroup analysis according to time since last peritonitis (<3, <6, >6 months). In patients with more than 24 months of PD vintage, submesothelial thickness, vessel number per mmm section length and ASMA fibroblast positivity were higher in patients with peritonitis history; only the difference in ASMA positivity persisted in multivariable analyses. While PD duration and EMT were independently associated with submesothelial thickness, and glucose exposure and EMT with peritoneal vessel density in the combined groups, submesothelial thickness was independently associated with EMT in the peritonitis free patients, and with duration of PD in patients with previous peritonitis. This detailed analysis of the peritoneal membrane in pediatric patients on PD with neutral pH, low GDP fluids, does not support the notion of a consistent long-term impact of peritonitis episodes on peritoneal membrane ultrastructure, on inflammatory and fibrotic cell activity and EMT. Peritoneal alterations are mainly driven by PD duration, dialytic glucose exposure, and associated EMT.
腹膜透析(PD)相关腹膜炎对腹膜完整性的影响尚未完全明确。儿童特别适合解决这个问题,因为他们基本上没有预先存在的组织损伤和与生活方式相关的改变。在国际腹膜生物样本库中,从82名使用低葡萄糖降解产物(GDP)含量的中性pH值腹膜透析液的儿童中获取了85份标准化的壁层腹膜组织样本。37例患者有腹膜炎病史,其中16例有两次或更多次发作。组织采样与最后一次腹膜炎发作之间的时间间隔为9(4,36)周。组织标本进行了数字成像和分子分析。有和无腹膜炎的患者分别接受腹膜透析21.0(12.0,36.0)个月和12.8(7.3,27.0)个月(P = 0.053)。他们在人体测量或组织形态计量学参数[间皮覆盖、间皮下纤维化、血液和淋巴管生成、白细胞、巨噬细胞和活化成纤维细胞计数、上皮-间质转化(EMT)、血小板内皮细胞黏附分子阳性和血管病变]方面没有差异。VEGF和TGF-β诱导的pSMAD丰度相似。在根据年龄和腹膜透析病程进行匹配以及根据自上次腹膜炎以来的时间(<3、<6、>6个月)进行亚组分析后,也得到了类似的结果。在腹膜透析病程超过24个月的患者中,有腹膜炎病史的患者间皮下厚度、每平方毫米切片长度的血管数量和α-平滑肌肌动蛋白(ASMA)成纤维细胞阳性率更高;只有ASMA阳性率的差异在多变量分析中仍然存在。虽然在合并组中腹膜透析持续时间和EMT与间皮下厚度独立相关,葡萄糖暴露和EMT与腹膜血管密度独立相关,但在无腹膜炎的患者中间皮下厚度与EMT独立相关,在有既往腹膜炎的患者中与腹膜透析持续时间独立相关。对使用中性pH值、低GDP液体进行腹膜透析的儿科患者的腹膜进行的详细分析不支持腹膜炎发作对腹膜超微结构、炎症和纤维化细胞活性以及EMT有一致的长期影响这一观点。腹膜改变主要由腹膜透析持续时间、透析葡萄糖暴露和相关的EMT驱动。