| Popis: |
Conventional hemodialysis (HD) and peritoneal dialysis (PD) for patients with end stage kidney disease (ESKD) have major shortcomings. Removal of waste molecules and excess fluid is inadequate, contributing significantly to poor life quality, high morbidity and high mortality. Increasing the dialysis dose would be a major improvement in renal replacement therapy. A miniaturized dialysis device with reuse of spent dialysate can facilitate longer and more frequent dialysis. In addition, a miniaturized design that is independent of a fixed water supply because of dialysate regeneration will offer more freedom and autonomy to the patient. In designing such a device, effective removal strategies must be developed for removal of all uremic waste products, excess sodium and water. In this thesis, we showed that we were able to develop a miniature dialysis device that can remove considerable amounts of excess potassium, phosphate and urea by using sorbents for electrolyte balance and electro-oxidation (EO) for urea removal from spent dialysate. First, we selected sodium poly(styrene-divinylbenzene) sulfonate beads for potassium removal and iron oxide hydroxide beads for phosphate removal. These sorbents showed potent potassium and phosphate removal, no net calcium and magnesium removal when preloaded with these electrolytes and were also excellently regenerable. Regenerability was a major selection criterion since the possibility to regenerate spent sorbents would considerably lower exploitation costs of a miniaturized dialysis device. Second, we selected graphite electrodes for urea removal by EO since they had the best ratio between urea degradation and generation of toxic chloride oxidation by-products. Third, we validated the results of our in vitro experiments in vivo in a large animal (goat) model. We documented potential toxic side effects of the selected sorbents and EO and tested measures to correct these by effects. In addition, we showed in vitro that mixed matrix membranes, dialysis membranes with integrated activated carbon particles, could be an asset in the optimization of protein bound uremic toxin removal in a miniature dialysis device as well as in conventional HD. The research performed in this thesis paves the way for further testing of a miniature dialysis device and, in the long term, this will facilitate longer and easier dialysis at home for a larger proportion of the patients with ESKD requiring dialysis. |
