Magnus Braide research group
Peritoneal dialysis (PD) is an established replacement therapy in the treatment of end stage renal disease. It is based on the semi-permeable properties of the peritoneal membrane, allowing exchange between the circulation and an osmotically active PD fluid present in the peritoneal cavity. Compared with hemodialysis, PD offers several advantages. A major disadvantage of PD is a deterioration of the peritoneal membrane in a fraction of the PD patients.
My project is focused on the pathophysiology of PD, i.e. how local responses (e.g. inflammation) to PD fluids interact with the transperitoneal transport processes that determine PD performance over time. In recent years we have characterized the acute and chronic peritoneal reactions to fluids, showing involvement of the intraperitoneal complement and coagulation systems. We have demonstrated that the acute inflammatory response modifies the transperitoneal transport during experimental PD. Studies along this line of evidence lead to the introduction of the calcium chelator citrate as a complement blocker that improves PD performance in rats and humans.
Citrate-based PD fluids are now subject to further studies of safety and dose response in order to prepare for clinical trials and commercialization.
The citrate studies also lead to the discovery that mechanical / osmotic stimulation caused by PD fluid exposure induced acute neurogenic inflammation and released neuropeptides interacted with microvascular tone and permeability. Blocking of neuropeptides SP and CGRP significantly affected plasma albumin loss and improved PD performance.
The project is now continued in two directions: Firstly, studies of the mechanisms of action of citrate based PD fluids prepare for clinical evaluations of new PD fluids. Secondly, neurogenic inflammation, triggered by mechanosensing is studied in a wider perspective, including reactions to soft tissue implants and post-surgical adhesion formation.
Farhan Bazargani, PhD 050316 “Acute inflammation in peritoneal dialysis: experimental studies in rats”
Maria Hägg, PhD 080508 ”Hypoxia-inducible factors (HIFs) and biological responses in hypoxia, inflammation and embryonic vascular development”
Nicola Cavallini, PhD 091013 ”Acute and chronic peritonitis in peritoneal dialysis: neurogenic inflammation and citrate treatment”
Professor Börje Haraldsson, department of Nephrology, Sahlgrenska University Hospital, Gothenburg