Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba 81531-980, Brazil.
Laboratory of Cardiovascular Immunology, Center of Natural and Human Sciences (CCNH), Federal University of ABC, Santo André 09210-580, Brazil.
Toxins (Basel). 2021 Nov 4;13(11):778. doi: 10.3390/toxins13110778.
Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.
心肾综合征(CRS)被描述为心脏原发性功能障碍,最终导致肾脏损伤,或者反之亦然。CRS 可分为五组,所有类型的 CRS 都观察到尿毒症毒素(UT)积聚。蛋白结合尿毒症毒素(PBUT)的积聚是对肾脏组织造成永久性损伤的原因,主要发生在 CRS 类型 3 和 4 中,从而直接损害肾功能,导致肾小球滤过率(GFR)下降和/或随后的蛋白尿。随着 GFR 的下降,患者可能需要肾脏替代治疗(RRT),如腹膜透析(PD)。PD 是一种针对终末期肾病(ESRD)患者的高质量、家庭为基础的透析治疗方法,基于腹膜的半透性特点。这些患者会接触到可能导致腹膜发生多种变化的因素。UT 的存在可能会损害腹膜膜,从而导致细胞外囊泡(EVs)的形成。EVs 几乎可以由所有细胞类型释放,并且包含源自其细胞的脂质、核酸、代谢物、膜蛋白和胞质成分。我们的研究小组之前证明,EVs 可能与内皮功能障碍有关,并且当 UT 与内皮单层接触时形成。在这种情况下,本综述探讨了 CRS、尿毒症、腹膜中 EV 形成的机制,以及作为腹膜透析中潜在的生物标志物。