# The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge
## 1 Introduction
### Current Extracorporeal Purification between Limitations and New Perspectives  
Current hemodialysis techniques include hollow-fibered dialyzers that replaced the original giant rotating drum kidney and represent today essential therapeutical options for patients admitted to hospitals with acute kidney injury (AKI) or ESKD. Although these devices have been shown to extend the lives of patients, the existing blood purification technology is still not perfect, being based only on processes of removing molecules from the patient's blood. New technology is needed to overcome the shortcomings represented by the patient's quality of life, intra-hemodialysis issues, and the still unmatched replacement of kidney metabolic functions. Although the available blood deprivation system has improved in terms of effectiveness, efficiency, and biocompatibility, the principles of blood purification have not changed from the first generation of artificial kidneys. From this point of view, the main targets of dialyzers are solute clearance and fluid removal from the patient without providing molecule reabsorption, catabolism, and endocrine function which are active functions that can be performed by a more complex system than the dialysis filter. Bioengineering has developed a specific blood purification technology to achieve the removal of molecules retained during ESKD based on the specific dialyzer structure, performance, biocompatibility, and membrane material. Thus, research in this area is directed toward finding devices that are increasingly efficient in removing target molecules but without finding viable solutions in the area of reabsorption and secretion of specific molecules. Artificial kidneys and semipermeable membranes for blood purification are still a current matter of research. Due precisely to their future characteristic of being bioartificial, artificial kidneys could significantly implement extracorporeal purification by introducing the activities of secretion, reabsorption, and metabolic activity. The advances in synthetic membranes, nanotechnology, and experience in dialysis have contributed to the potential of forthcoming dialyzer development; in fact, it took decades to develop the system of blood purification currently in use. Nowadays, such development allowed the move from regular dialysis for ESKD to Continuous Kidney Replacement Therapy (CKRT) in the Intensive Care Unit (ICU). The ability to have advanced and safe software and hardware to perform CKRT allows us replacement of renal function in a continuous way especially in highly critical and unstable patients that require continuous adjustment of renal metabolic compensation to their clinical needs. Despite these technological implementations, a lot of work is still to be conducted in order to improve the three major drawbacks of current hemodialysis techniques: patients' quality of life, technical problems that may occur during dialysis treatment, and the impossibility of replacing the kidney's metabolic functions [3]. The most important aspect that should lead the development of the new generation of artificial organs is that natural kidneys are not mere organs of filtration. As a matter of fact, they are also in charge of several metabolic functions, such as the synthesis of 1,25-dihydroxyvitamin D (1,25(OH)\({}_{2}\) D) [4], ammonia genesis [5; 6], glutathione metabolism [7], erythropoietin production [8], and immunoregulatory support [9]. Thus, to truly fulfill every kidney function, the renal metabolic role is to be taken into consideration. In fact, modern designs of artificial kidneys put much emphasis on the efficiency of dialysis and fluid removal but not on its metabolic functions. From a clinical point of view, this lack of metabolic activity requires the use of specific drugs that must be administered to the patient according to a biochemical feedback that has to be regularly checked with blood tests.