Bartosova Maria, Zarogiannis Sotirios G, Schmitt Claus Peter
Center for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
Department of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Mol Cell Pediatr. 2022 May 5;9(1):9. doi: 10.1186/s40348-022-00141-3.
Children with chronic kidney disease (CKD) suffer from inflammation and reactive metabolite-induced stress, which massively accelerates tissue and vascular aging. Peritoneal dialysis (PD) is the preferred dialysis mode in children, but currently used PD fluids contain far supraphysiological glucose concentrations for fluid and toxin removal and glucose degradation products (GDP). While the peritoneal membrane of children with CKD G5 exhibits only minor alterations, PD fluids trigger numerous molecular cascades resulting in major peritoneal membrane inflammation, hypervascularization, and fibrosis, with distinct molecular and morphological patterns depending on the GDP content of the PD fluid used. PD further aggravates systemic vascular disease. The systemic vascular aging process is particularly pronounced when PD fluids with high GDP concentrations are used. GDP induce endothelial junction disintegration, apoptosis, fibrosis, and intima thickening. This review gives an overview on the molecular mechanisms of peritoneal and vascular transformation and strategies to improve peritoneal and vascular health in patients on PD.
患有慢性肾脏病(CKD)的儿童会遭受炎症和反应性代谢产物诱导的应激,这会极大地加速组织和血管衰老。腹膜透析(PD)是儿童首选的透析方式,但目前使用的腹膜透析液含有远超生理水平的葡萄糖浓度,用于清除液体和毒素以及葡萄糖降解产物(GDP)。虽然CKD G5期儿童的腹膜仅表现出轻微改变,但腹膜透析液会引发众多分子级联反应,导致严重的腹膜炎症、血管增生和纤维化,其分子和形态学模式因所用腹膜透析液的GDP含量而异。腹膜透析还会加重全身性血管疾病。当使用高GDP浓度的腹膜透析液时,全身性血管衰老过程会尤为明显。GDP会导致内皮连接解体、细胞凋亡、纤维化和内膜增厚。本综述概述了腹膜和血管转变的分子机制以及改善腹膜透析患者腹膜和血管健康的策略。