# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 1 Introduction
### Current Extracorporeal Purification between Limitations and New Perspectives
Therapeutic adjustments are therefore subject to a constant delay due to the inability to have continuous online feedback as is the case with the metabolic activities of the natural kidney. Typical examples are changes in the dose and frequency of erythropoietin administration to maintain a constant hemoglobin in the patient, or the administration of vitamin D analogs to maintain proper bone metabolism. At present, the most effective approach to replacing organ function is the utilization of transplanted organs. Despite the limited organ availability and possible post-transplant complications, kidney transplantation remains the optimal treatment for ESKD. On the other hand, dialysis--both extracorporeal and peritoneal--is only life-sustaining and provides limited removal of uremic toxins. Despite the advances in technology, hemodialysis (HD) is still expensive, burdened by higher mortality, vascular access complications, and lesser quality of life and patient satisfaction compared with peritoneal dialysis, which, however, presents lower efficacy and a high risk of infections, which are the primary reason for transfer to HD [10]. Home hemodialysis (HHD) is believed to be more physiological and better tolerated by patients than in-center hemodialysis. Moreover, it has a number of advantages, including improved survival and quality of life (QOL), flexibility, and potential for employment compared to in-center hemodialysis [11; 12; 13; 14]. Technological research has moved towards the improvement and miniaturization of home hemodialysis services in order to overcome the constraints of standard HD with the development of new purification devices, such as novel dialyzers that mimic active processes of ultrafiltration and secretion in the native kidneys [15], membranes, wearable technology and sorbents for regenerating dialysate. These advances represent the first step towards the development of implanted devices capable of fully replacing natural renal function. The miniaturization of hemodialysis machines requires the development of advanced technologies that involve a multidisciplinary effort, including multiple clinical and technical elements such as vascular access, blood flow in the circuit, purification techniques, and catabolic and synthetic activity. Considering that at least 120 L of dialysate is required in a hemodialysis treatment, the regeneration of the waste fluid is necessary in order to allow the system downscaling into a portable device. The aim is to provide the elimination of substances through chemical breakdown and ion exchange [16; 17] or adsorptions to maintain electrolyte concentration within the normal range. Commonly, prolonged treatments, especially CKRT, can clinically result in excessive removals of ions that require their external supplementation as is the case for phosphate and potassium. This is reflected in an overload of work for nurses and a need for customization of treatments in terms of prescription, type of fluids used, and prescribed depurative dose. In a wearable/implantable device, this issue should be solved by intrinsic solutions in the device used minimizing external interventions by the physician, nurse, and patient. Specific devices can have an important role in this field not only to remove substances from dialysate, but also to exchange ions. The sorbent most commonly considered for this purpose is activated carbon. Historically, activated carbon was used in a home dialysis system that recirculated a 6 L batch of dialysate. Currently, the processing of spent dialysate by activated carbon (AC) is being considered to reduce the dialysate requirement for both hemodialysis and peritoneal dialysis. However, there is remarkably little research into the ability of activated carbon to remove different uremic solutes [18], in particular urea, that, in contrast to other organic waste compounds, binds poorly to sorbents (affinity for AC\(\sim\)0.1 mmol/g).