# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 1 Introduction
### Current Extracorporeal Purification between Limitations and New Perspectives
In addition, its amount is consistent, ranging from 240 to 470 mmol/day, making it the primary nitrogenous waste product of the metabolism [19]. The need to tailor the purifying dose to the individual metabolic needs of the patient plays an important role and represents a challenge for new implantable devices. According to the technology available for wearable miniaturized devices, urea removal can be obtained by the use of urease-catalyzed hydrolysis into bicarbonate and ammonium, which is more toxic than urea. In this case, zirconium phosphate may be used to remove ammonium by the dialysate; the bicarbonate released by hydrolysis, instead, reacts with protons to generate water and carbon dioxide, effectively removed from the dialysate closed-loop system [20]. Urea removal at the rate of 16 mmol/h is also possible, taking advantage of its electrochemical decomposition into N\({}_{2}\) and CO\({}_{2}\), which can be outgassed from the dialysate by using a device with reusable graphite electrodes [21]. Cartridge uptake could be another solution to urea removal in an effective, simple, and safe way. Sorbents can remove urea from dialysate either by forming covalent or coordination bonds (chemisorption) or by non-covalent bonds (van der Waals forces, dipole interactions, and hydrogen bonds, i.e., physisorption). However, in physisorption, even if the process is faster, the resulting bonds are weaker with sorbent-bound urea in equilibrium with urea dissolved in the dialysate, resulting in a lower removal efficiency [22]. Recent developments have shown the potential of sorbents for the effective removal of urea from the dialysate, among which are silicon dioxides (silica) and zeolites; however, aluminum leaching from zeolites is a potential hazard for the patient. All these solutions, although very interesting and fascinating from a technical point of view, still pose a whole series of limitations that make their use strictly experimental in prototypes that are unlikely to evolve into implanted and indomitable purification systems in the near future, although the wearable artificial kidney (WAK) could be a very promising way to provide a practical solution to the needs of patients. However, at present, only a few technical proposals have tried and are trying to achieve a realization of the WAK system to be used in clinical practice [15]. [PERSON] et al. demonstrated that treatment with the wearable artificial kidney was well tolerated, resulting in the maintenance of electrolyte and fluid homeostasis with effective uremic solute clearance. However, of the seven enrolled subjects, only five completed the planned 24 h treatment study. In fact, the trial was stopped because of device-related technical problems, such as excessive carbon dioxide bubbles in the dialysate circuit [16]. One of the most critical elements for extracorporeal purification in wearable devices is the ability to regenerate dialysate for long periods. Sorbent-based dialysate regeneration system has been effectively applied to the treatment of acute and chronic kidney failure patients for many years, and now it seems to have great potential in this research field. However, there are issues associated with the use of sorbents and resins to maintain the pH and electrolytic composition of the dialysate in the range required by the patient's clinical condition. In their preliminary report, [PERSON] et al. [16] demonstrated that patients tolerated this treatment very well and were allowed eating and drinking, as about 1 L of water was removed by ultrafiltration, with no significant change in blood pressure. Moreover, they demonstrated patient feedback in terms of a lack of interdialytic symptoms and a minimal to zero recovery time post treatment; patients were equally positive in their perception of the therapeutic potential of this device in terms of facilitating treatment flexibility, freedom, and improved lifestyle.