Targeting metabolism to improve the host response to peritoneal dialysis

慢性肾脏疾病（CKD）是一个主要的健康问题，影响着多达12%的人口，并且在全球范围内呈上升趋势。血液透析是主要的治疗方法，它给医疗系统带来了持续的压力，移植的速度跟不上需求，并不是每个病人都有资格进行移植。因此，家庭腹膜透析（PD）越来越多地被用作一种更好的选择，无论是在经济上还是在生活质量上，因为它限制了住院时间，给了患者更多的自由。不幸的是，PD目前还不是一种永久性的治疗选择；并发症可能出现，如腹膜感染（腹膜炎）和免疫细胞驱动的纤维化（腹膜瘢痕）。因此，研究免疫细胞在PD中的功能可能会提高治疗的寿命，减轻卫生系统的负担，提高患者的生活质量。PD的功能是通过腹膜导管向腹膜腔注入约2升透析液，透析液是糖和稳定剂的基本混合物，仅用于从血液中提取废物代谢物。我之前的研究表明，腹膜中重要的免疫细胞需要更广泛的代谢物来发挥其抗微生物功能，包括谷氨酸等氨基酸。目前，PD中尚未考虑免疫细胞的健康和功能。本项目将研究PD液的代谢物改变（如谷氨酸的添加）对促进细胞健康和免疫防御的益处，从而预防PD的不良后果。本项目的目标是确定腹膜透析液的最佳添加剂，以提高患者的治疗寿命，并确定改变免疫细胞的代谢是否可以治疗腹膜炎。

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.