Clinical, Experimental and Theoretical Studies of Solute and Water Removal in Peritoneal Dialysis

Peritoneal dialysis (PD) is a cost-effective, home-based kidney replacement therapy that enhances patient autonomy. Nevertheless, the clinical use of PD is limited by chronic fluid overload and excessive glucose absorption, which can lead to complications, such as cardiovascular disease, metabolic disturbances, and deterioration of the peritoneal membrane.
The aims of this thesis were to examine glucose transport mechanisms across the peritoneum and develop a robust, clinically applicable test for assessing membrane transport properties for both solutes and water. This would enable personalized treatment strategies and facilitate the long-term monitoring of membrane changes, potentially improving patient outcomes and extending the viability of PD as a treatment modality.
Study I showed that acute inhibition of SGLT2 transporters caused well-known effects, such as glycosuria and reduced plasma glucose levels, but did not significantly affect glucose absorption or osmotic water transport across the peritoneum during experimental PD.
Study II demonstrated that phloretin, a non-selective blocker of facilitative glucose channels (GLUTs), and ritonavir, a GLUT1/GLUT4 blocker, reduced the diffusion of the glucose analog, [18F]-deoxyglucose, and improved ultrafiltration. However, selective GLUT1 and GLUT4 blockers had no significant effect on [18F]-deoxyglucose or glucose transport. Reduced [18F]-deoxyglucose clearance during GLUT inhibition suggests that glucose absorption during PD occurs transcellularly across the peritoneal cells.
Study III demonstrated that residual volume significantly impacts measurement of osmotic conductance to glucose (OCG) and the reliability of these results. A new and more accurate OCG measurement method was developed.
Study IV successfully improved and validated a combined peritoneal equilibration (CombiPET) test for measuring OCG and peritoneal solute transport properties in patients with PD, showing accurate and reproducible results across repeated tests.
In conclusion, the new, simple, and reliable CombiPET method for assessing water and solute transport across the peritoneal membrane will facilitate clinical decision making and save time for patients and healthcare professionals. Although SGLT2 inhibitors, such as empagliflozin, did not affect glucose absorption or ultrafiltration, facilitative glucose channels seem to play a significant role in glucose transport during PD.