# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 1 Introduction
### Current Extracorporeal Purification between Limitations and New Perspectives
The clinical subjective impact of such technology appears to be positive, with patients' perception that the system is safe and easy to use in daily life. These findings confirm that by redesigning to address the identified technical issues, a wearable artificial kidney can be successfully created as an innovative and feasible alternative to traditional dialysis technology. An ideal implantable bioartificial kidney could overcome the problem of dialysate regeneration by mimicking the full renal function. This could be achieved by combining bioreactors and blood ultrafiltration to replicate key native cell functions for solute reabsorption, secretion, and endocrinologic activities (1,25-OH-vitamin D and erythropoietin production). In order to mimic the complex renal functions and to achieve fluid balance and waste removal [23] by filtration and secretion, the implantable bioreactor needs to be combined with an ultrafiltration system. This ensures the reabsorption of useful molecules such as bicarbonate, amino acids, glucose, and phosphate. In the context of nephrology, and specifically in the field of extracorporeal blood purification, a bioreactor can be defined as a specialized device designed to support the growth, maintenance, and function of renal cells or tissues in a controlled environment to mimic the physiological kidney function to provide a platform for blood purification to improve dialysis technology development with metabolic and molecule reabsorption and secretion activities. In a nutshell, the future of artificial kidneys aims at miniaturization and implantability, better biocompatibility, and metabolic function combining all available technology. It is undoubted that membranes are the fulcrum of extracorporeal treatment, and technological advances in membrane design, chemical composition, and sterilization methods lead to enhanced performance with the reduction of dialysis \"unphysiology\". Modifications of the composition of HD membranes have improved their biocompatibility and improved patient quality of life. Specifically, membranes composed of polymeric or inorganic material appear to be more efficient for the removal of uremic toxins compared to synthetic membranes. However, membranes utilized for hemodialysis are efficient in the removal of small water-soluble solutes and toxins, but their efficiency decreases proportionally for middle to large molecules and toxins. Protein-bound uremic toxins are also hard to remove. Ideally, membranes have to mimic glomerular filtration [24] with molecular weight cut-offs up to ~66 kDa [25]. The prolonged use of these membranes, while mimicking the continuous kidney filtration, leads to issues such as biocompatibility and filter patency, becoming a further challenge for the development of implantable devices. In order to implement biological functions and purification efficacy, the novel membranes could be combined with bioartificial kidneys, where artificial membranes are combined with kidney cells in bioreactors. To overcome the shortcomings of current devices for artificial kidneys, studies and trials of silicon nanopore membranes, tissue engineering for renal cell bioreactors, and dialysate regeneration are under development. With future advancements, wearable or implantable artificial kidneys will be soon achievable [26]. The feasibility of an implantable bioreactor for renal cell therapy was demonstrated by [PERSON] et al. [27], opening the challenge to the development of a completely implantable bio-artificial kidney (iBAK). Such a device is based on silicon nanopore membranes that ensure immunological isolation, cell viability, and the possibility of maintaining a blood substrate for metabolic activities. Research in the field of membranes is developing new materials to overcome the limitation of blood purification in wearable and implanted devices due to the actual structural limitation of classical dialyzers.