College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Perit Dial Int. 2019 Jul-Aug;39(4):362-374. doi: 10.3747/pdi.2018.00052. Epub 2019 May 23.
Infectious peritonitis is a clinically important condition contributing to the significant mortality and morbidity rates observed in peritoneal dialysis (PD) patients. Although some of the socioeconomic risk factors for PD-associated peritonitis have been identified, it is still unclear why certain patients are more susceptible than others to infection.We examined the molecular components of human peritoneal dialysate (HPD) in an attempt to identify factors that might increase patient susceptibility to infection. Characterization studies were performed on initial and follow-up dialysate samples collected from 9 renal failure patients on PD.Our data showed that peritonitis-causing bacteria grew differently in the patient dialysates. Proteomic analysis identified an association between transferrin presence and infection risk, as peritoneal transferrin was discovered to be iron-saturated, which was in marked contrast to transferrin in blood. Further, use of radioactive iron-labeled transferrin showed peritoneal transferrin could act as a direct iron source for the growth of peritonitis-causing bacteria. We also found catecholamine stress hormones noradrenaline and adrenaline were present in the dialysates and were apparently involved in enhancing the growth of the bacteria via transferrin iron provision. This suggests the iron biology status of the PD patient may be a risk factor for development of infectious peritonitisCollectively, our study suggests transferrin and catecholamines within peritoneal dialysate may be indicators of the potential for bacterial growth in HPD and, as infection risk factors, represent possible future targets for therapeutic manipulation.
感染性腹膜炎是一种临床上重要的病症,可导致腹膜透析(PD)患者的死亡率和发病率显著升高。尽管已经确定了一些与 PD 相关腹膜炎的社会经济风险因素,但仍不清楚为什么某些患者比其他患者更容易感染。我们研究了人腹膜透析液(HPD)的分子成分,试图确定可能增加患者易感性的因素。对 9 名 PD 患者的初始和随访透析液样本进行了特征描述研究。我们的数据表明,引起腹膜炎的细菌在患者透析液中的生长方式不同。蛋白质组学分析表明,转铁蛋白的存在与感染风险之间存在关联,因为腹膜转铁蛋白被发现是铁饱和的,这与血液中的转铁蛋白形成鲜明对比。此外,放射性铁标记转铁蛋白的使用表明,腹膜转铁蛋白可以作为引起腹膜炎的细菌生长的直接铁源。我们还发现去甲肾上腺素和肾上腺素等儿茶酚胺应激激素存在于透析液中,显然通过转铁蛋白铁供应来增强细菌的生长。这表明 PD 患者的铁生物学状态可能是发生感染性腹膜炎的一个风险因素。综上所述,我们的研究表明,腹膜透析液中的转铁蛋白和儿茶酚胺可能是 HPD 中细菌生长潜力的指标,作为感染的风险因素,它们可能成为未来治疗干预的潜在靶点。