PERITONEAL MEMBRANE SOLUTE TRANSPORTER EXPRESSION AND FUNCTION IN HEALTH, CHRONIC KIDNEY DISEASE AND PERITONEAL DIALYSIS
Lévai Eszter
Clinical Medicine
Dr. Fekete Andrea
SE I. Gyermekgyógyászati Klinika tanterme
2025-09-30 14:00:00
Prevention of Chronic Diseases in Childhood
Dr. Szabó Attila
Dr. Szabó Attila
Dr. Pethő Ákos
Dr. Berkes Andrea
Dr. Benyó Zoltán
Dr. Fenyves Bánk
Dr. Balla József
Dr. Geiszt Miklós
This dissertation outlines the novel importance of paracellular transport proteins as molecular counterparts of peritoneal membrane function, important in peritoneal dialysis, an optimal renal replacement therapy in ESRD, an increasingly common state worldwide, leading to major cardiovascular complications, a reduced life-expectancy and placing a heavy burden on healthcare systems.
By proving consistent detectability and describing the changes of distinct sealing, pore-forming and scaffolding TJ proteins (CLDN1-5, and CLDN15, ZO-1, OCL, TriC) and a few transcellular transporters and channels (PiT1, SGLT1, ENaC), the probable role of these molecules in peritoneal membrane changes during PD was pointed out. Description of mesothelial abundances and changes prepared further functional studies of our group to emphasize the role of the mesothelium as a barrier in peritoneal solute transport. (9)
Finding associations of target TJ molecules and peritoneal membrane transport functional data highlights CLDN2, CLDN4, CLDN15 and PiT1 as possible target molecules for future interventions to enhance PD function.
To standardize and enhance studying barrier integrity, permeability and TJ composition, localization and clustering in a single monolayer, a new experimental workflow was established. Thus, maximizing the retrievable coherent information content from a single monolayer, making it possible for future investigators to provide a triad of functional, temporal and spatial description of paracellular permeability changes, with particular regard to effects on the TJs.
Opening up a window to PD fluid additive research AlaGln was tested and proven to seal the epithelial barrier. Dialysis fluids affect TJ organization by disruption, which can be counteracted by AlaGln through increasing transepithelial resistance and decreasing small and middle molecule transport. Increased CLDN5 and ZO-1 abundance was present with AlaGln supplementationd to CPDF and AlaGln also improved the clustering of ZO-1 in the endothelial membrane. This example of targeting the molecular basis of peritoneal transport is a key to improve PD efficacy and patient outcome.
To address further complications of PD treatment and therefore provide a new interface of interventions to molecular counterparts of the endothelial barrier, a link between GDP load and systemic vasculopathy was established. GDP induces endothelial cell junction and cytoskeleton disruption, next to the induction of apoptosis. This finding is crucial for prevention of long-term cardiovascular complications in PD patients, especially children on chronic PD.
