Optimization and Study of Biomedical Materials and Devices for Renal Replacement Therapies and Haemodialysis

The kidneys perform numerous essential regulatory functions, including the ability to purify the blood, maintain electrolyte balance and a physiological pH, and when these are no longer properly carried out, acute kidney injury (AKI) appears, a clinical condition that represents a risk factor for morbidity and mortality, which causes the death of about 2 million people per year and whose long-term effects lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There are several renal replacement therapies (RRT), the most widely used is Continuous Renal Replacement Therapy (CRRT) which, through an extracorporeal circuit which includes a semipermeable filter, allows removal rates of solutes and toxins in a continuous, gradual and slower way compared to intermittent haemodialysis, thus closely approaching the physiological condition. The evaluation of filter performance, intended as the ability to remove specific solutes and biomarkers, is essential to optimize treatment and personalize therapy. Hematica srl is a company whose activity aims at developing an integrated device for the real-time monitoring of filters performances during CRRT. The present thesis, which was carried out within this company, focuses on the research for a panel of solutes which are able to mirror the variation of filters performances. Moreover, a literature review and market analysis for the search of a suitable technology and device for the real time quantification of these solutes was performed. Finally, an experimental set-up was implemented to simulate in vitro a CRRT treatment, and target solutes were analysed during the simulated therapy for a preliminary validation of solutes selection. In the first phase of the work, reference proteins were selected, identified on the basis of their clinical relevance, the data reported by the European Uremic Toxin Work Group (EUTox) and the scientific literature,. Subsequently, in collaboration with the University of Aquila, a database of about 4000 human plasma proteins (Human Protein Atlas) was used, implemented with a selection algorithm that assigns different weights to physicochemical parameters (molecular weight, volume, charge, sphericity), to carry out an additional exploratory screening, still ongoing, aimed, to further support the choice of the representative A second phase was dedicated to the review of traditional quantification technologies on the market and to the identification of new point-of-care (POC) devices, either under experimentation or commercially available, which would ideally present the following characteristics: high sensitivity and precision, low detection limits, ability to analyse complex matrices (blood, plasma, urine), compatibility with small sample volumes, rapid response (real-time) and multiplex detection. Evaluations are underway with industrial partners for the development of dedicated electrochemical biosensors. In parallel, a commercial POC device (Finecare®, based on immunofluorescence) was purchased and tested in comparison with a gold standard (COBAS800, Roche®) in Careggi Hospital (Florence). The CRRT simulation experiments were carried out in collaboration with Careggi Hospital in Florence, and biological samples were analysed at the central laboratory, allowing a preliminary evaluation of membrane performance.