Targeting metabolism to improve the host response to peritoneal dialysis

靶向代谢以改善宿主对腹膜透析的反应

• 批准号: MR/Y013816/1
• 负责人: Luke Davies
• 金额: $ 82.13万
• 依托单位: Swansea University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY013816%2F1
• 关键词: Targeting; metabolism; improve; host; response

Chronic Kidney Disease (CKD) is a major health problem which affects up to 12% of the population and is on the rise globally. The primary treatment, haemodialysis puts constant pressure on healthcare systems, the speed of transplants cannot keep up with demand and not every patient is eligible for a transplant. Therefore, at-home peritoneal dialysis (PD) is increasingly used as a better option, both financially and for quality of life, as it limits time in hospital and gives patients more freedom. Unfortunately, PD is not currently a permanent treatment option; complications can arise, such as peritoneal infections (peritonitis) and immune cell-driven fibrosis (scarring of peritoneal membranes). Therefore, research that addresses the function of immune cells in PD is likely to improve the longevity of treatment, decrease the burden on health systems and improve the quality of life of patients. PD functions by using a peritoneal catheter to fill and drain the peritoneal cavity with approximately 2 litres of dialysis fluid - a basic mixture of sugar and stabilisers designed only to draw waste metabolites from the blood. My previous research has shown that vital immune cells in peritoneum require a broader range of metabolites to perform their anti-microbial function, including amino acids such as glutamate. Currently, the health and function of immune cells are currently not considered in PD. This project will investigate the benefits of metabolite alteration of PD fluid (e.g. addition of glutamate) to promote cell health and immune defence, which will prevent the poor outcomes of PD. The goals of this project to define the best additives for peritoneal dialysis fluid that improves the longevity of this treatment option for patients, and to determine whether altering the metabolism of immune cells can treat peritonitis.

慢性肾脏疾病（CKD）是一个主要的健康问题，影响多达12％的人口，并且在全球范围内正在增加。血液透析的主要治疗方法会持续压力医疗系统，移植速度无法跟上需求，并不是每个患者都有资格进行移植。因此，由于它限制了医院的时间并为患者提供更多的自由，因此越来越多地将在家腹膜透析（PD）用作更好的选择，无论是经济上还是为了生活质量。不幸的是，PD目前不是永久治疗方案。可能会出现并发症，例如腹膜感染（腹膜炎）和免疫细胞驱动的纤维化（腹膜膜的疤痕）。因此，解决PD免疫细胞功能的研究可能会改善治疗的寿命，减轻卫生系统的负担并改善患者的生活质量。 PD通过使用腹膜导管用约2升透析液填充和排干腹膜腔的功能 - 糖和稳定剂的基本混合物仅用于从血液中抽取废物代谢物。我以前的研究表明，腹膜中的重要免疫细胞需要更广泛的代谢物来执行其抗微生物功能，包括谷氨酸等氨基酸。当前，PD中目前尚未考虑免疫细胞的健康和功能。该项目将研究PD液（例如添加谷氨酸）代谢物改变的好处，以促进细胞健康和免疫防御，这将防止PD的不良预后。该项目的目标是定义腹膜透析液的最佳添加剂，以改善患者的治疗选择的寿命，并确定改变免疫细胞代谢是否可以治疗腹膜炎。