Brocca Alessandra, Virzì Grazia Maria, Pasqualin Chiara, Pastori Silvia, Marcante Stefano, de Cal Massimo, Ronco Claudio
Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Via Rodolfi 37, 36100 Vicenza, Italy ; Department of Medicine DIMED, University of Padova Medical School, Via Giustiniani 2, 35100 Padova, Italy ; Laboratory of Experimental Hepatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35100 Padova, Italy.
Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Via Rodolfi 37, 36100 Vicenza, Italy.
Anal Cell Pathol (Amst). 2015;2015:469461. doi: 10.1155/2015/469461. Epub 2015 Jul 22.
Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients.
背景。5型心肾综合征(CRS 5型)反映了在多种全身性疾病背景下心脏和肾脏的功能障碍并存。我们的目的是研究CRS 5型血浆对肾小管细胞(RTCs)的体外影响,包括细胞死亡情况以及这些患者炎症性血浆谱的特征。材料与方法。我们纳入了11名来自重症监护病房(ICU)的CRS 5型患者和16名健康对照者。将患者和对照者的血浆与肾小管细胞(RTCs)共同孵育,并评估细胞死亡情况。检测血浆细胞因子。结果。与对照组相比,用CRS 5型血浆孵育的RTCs显示出明显更高的凋亡和坏死率。CRS 5型患者的血浆细胞因子谱与对照组有显著差异:我们观察到这些患者体内促炎和抗炎介质的产生。与对照组相比,用CRS 5型血浆处理的细胞中半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9被激活。结论。我们的结果强调了CRS 5型介质对RTC活力的细胞毒性作用,这可能是由于凋亡的内源性和外源性途径均被激活以及细胞因子释放失调所致。其后果可能是远处器官的损伤,导致患者病情恶化。