Mechanisms of Peritoneal Water and Solute transport - Computational Modelling and Clinical Implications

Peritoneal dialysis is a widely used, cost-effective and accessible renal replacement therapy. Theprimary aim of this thesis is to study and measure the mechanisms that govern fluid and electrolytetransport in peritoneal dialysis by combining theoretical models with experiments on rats and analysisof clinical datasets. Despite the apparent simplicity of the treatment, the physiological mechanisms thatgovern the transport of solutes and water are highly complex.In study 1, we investigate the effects of very high ultrafiltration rates on blood plasma volume.Experimental peritoneal dialysis was performed on rats using dialysis fluid with a very high glucosecontent, and plasma volumes were measured using albumin with a radioactive tracer technique.Plasma volumes appeared unchanged despite high ultrafiltration rates.The aim of study 2 was to validate and test a new mathematical model for estimating ultrafiltration ratein peritoneal dialysis from the phenomenon known as the sodium dip. The model was testedexperimentally on rats, by estimating ultrafiltration rates during peritoneal dialysis using the new modeland a reference method. Then, the same analysis was performed on a cohort of patient data. Resultsshowed excellent agreement between ultrafiltration estimates obtained with the new method and thereference method in experimental data, and moderate agreement in clinical data. The same was truefor osmotic conductance to glucose in clinical data.Finally, in study 3, the well-established three-pore model for peritoneal transport was modified by usingthe Nernst-Planck equation to describe electrolyte transport. The model was fitted to experimental datafrom peritoneal dialysis performed on rats, by using the kinetics of sodium to estimate hydraulicconductance and area-to-diffusion length ratio. After incorporating the parameters, the modelindependently predicted the transport of water and solute species other than sodium.