Analysis of Point-of-Care Technologies for Monitoring CRRT Therapies: a Technological and Regulatory Approach

Acute Kidney Injury (AKI) is a condition that occurs in critically ill patients when renal dysfunction prevents the elimination of waste products from the blood. When this happens, harmful levels of waste may build up, and the blood chemicals may get out of balance. Patients who suffer from AKI undergo hemodialysis, a form of continuous renal replacement therapy (CRRT), that can last up to 72 hours. During this process, the blood is purified through a filter, called the dialysis membrane, whose porous structure allows the removal of waste solutes. To verify the effectiveness of the therapy, the healthcare professionals should perform blood samplings from different sites in the extracorporeal circuit to analyse solute concentrations. This process, however, proves to be inefficient, since it would require the simultaneous presence of multiple healthcare operators to do the sampling. This could lead to potential errors in timing and synchronisation that may compromise the validity of the results. Furthermore, during therapy, solutes can be trapped in the membrane, resulting in a process known as membrane fouling. This can alter the value of the effective delivered dose, which represents the actual solute clearance. In this context, Hematica s.r.l. developed a device that automatically withdraws the blood samples from the three accesses of the extracorporeal circuit. The primary objective of this Master's Thesis is to assist in drafting the documentation required to submit an application to the Ministry of Health regarding the clinical investigation for the developed device. After the sampling, a challenge affecting real-time filter monitoring is the quantification of the target solutes, since the laboratory analysis can take several hours for the results, further delaying clinical assessment. Currently, there is no technology that can analyse multiple blood renal markers of different dimensions in real time. Point-of-care (POC) devices, therefore, represent a new frontier in analytical diagnostics, due to their compactness, portability, and ability to provide laboratory-quality results within a short time. The second purpose of this thesis is to analyse the main commercial and research-level POC technologies currently available on the market for monitoring renal biomarkers, in order to evaluate the most promising solutions in terms of sensitivity, specificity, detection time, and validation level.