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INTRODUCTION Kidneys act as "filters" of metabolic waste in the human body, cleaning nearly 200 L of blood every day to maintain a homeostasis. Aberrant kidney function can cause the accumulation of metabolic wastes, resulting in imbalances in the water, electrolyte, and acid-base levels that may lead to varying symptoms, such as fatigue, dizziness, loss of appetite, anemia, and heart rate disorders. Approximately 800 million patients around the world have chronic kidney disease (CKD), which accounts for about 11%–13% of the global population.1 In end-stage renal disease (ESRD), which is the uremic stage of chronic renal insufficiency, most patients require renal replacement therapy (RRT), which is administered via maintenance hemodialysis, peritoneal dialysis, or kidney transplantation. CURRENT STATUS: RENAL REPLACEMENT THERAPY MODALITIES For patients with ESRD, RRT is essential for preserving life. It includes modalities such as kidney transplantation, maintenance hemodialysis, and peritoneal dialysis. Physicians aim to improve the prognosis and quality of life of their patients by offering individualized medical care; however, the comprehensive decision to select an RRT modality depends on the patient's condition, the indications and advantages of different treatment methods, and the choice of the patient and family members. The following Table 1 summarizes the respective characteristics of the different methods of RRT. Table 1 - The characteristics of different renal replacement therapy methods Modalities of RRT: Current Status Principles and Mechanisms Indications and Advantages Disadvantages Hemodialysis2 Ultrafiltration and diffusion •Main treatment method, suitable for most patients•Economical•Indicated for removal of uremic toxins, such as creatinine, urea, nitrogen, and uric acid •The aperture of the dialyzer is relatively small•Medium and large molecule toxins cannot be effectively filtered out High-flux hemodialysis3 Ultrafiltration, diffusion, and convection •More effective toxin removal than hemodialysis, especially for medium-to-large molecular substances •Reduces the occurrence of amyloidosis and carpal tunnel syndrome •Requires higher blood-flow rates•May need more nursing care and monitoring•Requires advanced equipment and technical support Hemofiltration4 Convection •Closer to physiological renal function•Better removal of medium-to-large molecular toxins•Minimal impact on cardiovascular function •Requires close monitoring of fluid and electrolyte balance during treatment•High demands in terms of quality of filtrate and replacement fluid Hemodiafiltration4 Diffusion and convection •Higher removal efficiency per unit time•Significantly better removal of medium-sized molecular toxins •Potential loss of nutrients•Requires close monitoring of physiological indicators during treatment Hemoperfusion5 Adsorption •Used for the specific conditions, such as drug poisoning and infectious diseases.•Improves clearance rate of specific toxins •Allergy to irrigators and related materials•Requires special equipment and expertise Continuous RRT6 Continuous blood filtration, dialysis, or hemodiafiltration •Suitable for critically ill patients•Has long-lasting treatment effects•Minimal impact on cardiovascular system•Effectively removes excess fluid and toxins •Continuous monitoring required during treatment•May require more complex equipment and specialized personnel support Peritoneal dialysis7 Diffusion and osmosis •Simple to use•Can be performed at home •Limited indications; not suitable for all patients•Requires certain skills and knowledge from patients or caregivers•Increased risk of complications, such as peritonitis and abdominal bleeding Kidney transplantation8 Transplanting donor kidney into recipient's iliac fossa •Effective treatment for end-stage renal disease•Can completely replace the work of the kidneys•Thoroughly clearing toxins •Long-term use of immunosuppressive agents increases the risk of infections and tumors•Limited availability of donors; requires waiting for matching and queuing•Requires rigorous postoperative monitoring to prevent rejection reactions In summary, hemodialysis removes excess fluid and toxins from the blood using a dialyzer. High-flux hemodialysis is more effective in eliminating medium-to-large molecular substances.9 Hemofiltration and hemodiafiltration use principles of convection and diffusion to clear toxins,10,11 whereas hemoperfusion is suitable for the specific removal of medium-to-large molecular toxins.12 Continuous RRT is indicated for critically ill patients.13,14 Peritoneal dialysis involves the exchange of substances across the peritoneum but is contraindicated in some cases. Kidney transplantation is an effective method, but it is limited by donor availability and the need for long-term immunosuppressive therapy.15 Therefore, selecting the appropriate treatment method should consider the specific needs and conditions of the patient. CHALLENGES: LIMITATIONS OF RRT Currently, the most commonly used RRT treatments for ESRD are hemodialysis and peritoneal dialysis; however, neither technique can completely replace all physiological functions of the kidneys. Peritoneal dialysis treatment is intermittent and has lower clearance efficiency. Hemodialysis is performed three times a week over 4-hour long sessions each time, whereas peritoneal dialysis fluid replacement is done 3–4 times a day, 2 L each time. Both treatments rely extensively on hospitals and medical care, generate large amounts of medical and fluid waste, and seriously affect the patient's quality of life and daily routine. Kidney transplantation is limited by a shortage of donors and requires the long-term use of immunosuppressants. As the number of patients with CKD is increasing, the medical community is calling for the development of disruptive RRTs, such as portable dialysis equipment, implantable artificial kidneys, and the invention of dialysis-related materials.16–20 The development of new technologies can transform the existing treatment model, enhance patients' quality of life, and eventually improve patient prognosis. BREAKING THE ICE: PROGRESS IN THE DEVELOPMENT OF NEW ARTIFICIAL KIDNEYS Recent research in the field of artificial kidneys encompasses a variety of technologies and equipment, including implantable artificial kidneys, wearable artificial kidneys, wearable peritoneal dialysis artificial kidneys, and 3D-printed artificial kidneys. The common goal of these technologies is to provide portable, flexible, and effective RRT and enhance patient outcomes. Next, this article will provide a brief overview of these technologies and summarize them in Table 2 to better understand their respective characteristics and advantages. Table 2 - Characteristics of new artificial kidney technology Technology Advantages Disadvantages Implantable artificial kidney •Simulates the functions of native glomerulus and renal tubules•Does not induce rejection reactions •Requires surgical implantation which is associated with risks•Needs periodic replacement of bioreactors•Risk of thrombus formation and other complications Wearable artificial kidney •Provides greater freedom for patients•Allows on-the-go dialysis with the use of a smartphone for monitoring •Requires establishment and maintenance of vascular access•Challenges in improving dialysis fluid regeneration and membrane technologies Wearable peritoneal dialysis artificial kidney •Light-weight and portable; suitable for daily wear•Treatment efficacy comparable to conventional peritoneal dialysis •Needs further improvement in dialysis fluid regeneration technology, materials, and miniaturization of the device Biological artificial kidney •Partial replacement of renal tubule function•Utilizes microfluidics and nanotechnology for miniaturization •Challenges in obtaining and manufacturing renal tubule epithelial cells 3D-Printed artificial kidney •Possesses glomerular and renal tubular filtration functions like the native kidney •Requires interdisciplinary collaboration•Still in the research stage with technological challenges abdomen and connected to blood vessels and the urinary bladder. Its unique feature is that it simulates the functions of the glomeruli and renal tubules. Although the technology does not cause tissue rejection, there are certain risks involved, such as thrombosis and the need for periodic replacement of bioreactors (Filter membrane made of silicon wafers). Implantable artificial kidney An implantable artificial kidney is a compelling medical innovation made of nanomaterials.18,21,22 This small device is similar in appearance to a chip and uses blood pressure to perform kinetic dialysis; it is surgically implanted in the patient's Wearable artificial kidney It is an important development in the miniaturization and mobility of hemodialysis technology.23,24 A wearable artificial kidney weighs approximately 2 kg, is worn via a belt, and uses batteries to perform kinetic dialysis. Compared to traditional dialysis therapy, it gives patients more flexibility in terms of the time and location of receiving dialysis without being confined by their surroundings. Both the patient and the doctor can conveniently monitor dialysis data through smartphones to achieve meticulous medical management. However, issues with the establishment and stability of vascular access, dialysate regeneration technology, and dialysis membrane improvement limit the use of this technology and require in-depth research and technological innovation. Wearable peritoneal dialysis artificial kidney It is a relatively lightweight dialysis device,25,26 weighing approximately 2 kg. Unlike traditional hemodialysis, it achieves therapeutic purposes through peritoneal dialysis, which is equivalent to conventional peritoneal dialysis. The technology is being developed rapidly and is expected to provide patients with more convenient and flexible dialysis options in the future. However, the materials and equipment used in dialysate regeneration technology are becoming smaller and more portable, which also brings challenges to process and technological innovation. Bioartificial kidney A bioartificial kidney (BAK) is an innovation in dialysis technology which combines synthetic materials with special renal tubular epithelial cells to partially replace renal tubular function.27–29 Renal-assist devices and implantable renal assist devices are representative miniature devices that have been developed using microfluidics and nanotechnology. However, there are certain challenges to the use of this technology in terms of the acquisition of renal tubular epithelial cells and the production process. 3D-printed artificial kidney The use of 3D printing technology to create living membranes and active kidney tissue for renal tubular function is a major breakthrough in the field of biomedical engineering.30,31 It includes bioprinting a nephron that mimics the physiological glomerular filtration functions to realize a mini-human kidney. However, various complex issues involved in the kidney printing process (such as printing fineness, whether bioactive substances can be printed, etc.) require interdisciplinary cooperation to solve. Some progress has been made in the research and development of artificial kidneys to improve the portability and dialysis efficiency of RRT and to augment the quality of life of patients; nevertheless, all technologies face challenges. BREAKTHROUGH: DEVELOPMENT OF WEARABLE PERITONEAL DIALYSIS TREATMENT EQUIPMENT Automated wearable artificial kidney (AWAK) is a leading medical innovation technology in which two products have been developed–AWAK-peritoneal dialysis (AWAK-PD) and AWAK-hemodialysis (AWAK-HD)–suitable for peritoneal dialysis and hemodialysis patients, respectively. Among these, AWAK-PD is particularly eye-catching due to its miniaturization and innovative dialysate regeneration technology.32 AWAK-PD is a small peritoneal dialysis equipment weighing only 2 kg. It uses approximately 1–2 L of dialysate, which is one-tenth of what is needed with traditional peritoneal dialysis since it employs neutral pH and a biocompatible dialysate. This is due to the proprietary cyclic dialysis adsorption technology used by AWAK-PD.33 Through this technology, AWAK-PD can excrete uremic toxins into the dialysate and regenerate dialysate, which means that patients can carry the AWAK-PD device with them, greatly improving the portability of the equipment and the feasibility of treatment. Studies have shown that patients' serum urea, creatinine, phosphorus, and β2-microglobulin levels were significantly reduced after AWAK-PD treatment, verifying the effectiveness of this technology.25 On average, the dialysate regeneration cycle of AWAK-PD is about one month, and the adsorbent cartridge needs to be replaced every 4–8 h. Lately, there has been ongoing research on similar miniaturized RRT equipment, and the technological breakthrough offered by AWAK-PD has made it the center of attention. The results of a safety and efficacy study regarding peritoneal dialysis using an AWAK-PD device in patients from a single center in Singapore conducted from 2016 to 2018 showed that no serious adverse events were observed with the device.25 However, 60% of participants experienced abdominal pain and discomfort, requiring further adjustments to the equipment to improve the comfort of the treatment process. AWAK's technological breakthrough is expected to bring benefits to dialysis patients, such as the freedom of availing treatment anytime and anywhere, a significant reduction in dialysate consumption, and an extended dialysate regeneration cycle. However, further research and equipment improvements are still needed before it can be used clinically to achieve the intended treatment effects while ensuring patient safety. CONCLUSION The emergence of mobile dialysis equipment has facilitated continuous and home dialysis for patients with ESRD; technological advances may allow the development of much smaller and more efficient dialysis machines and dialyzers. The evolution of BAK and functional 3D-printed human kidneys is a major breakthrough in medicine; however, the use of wearable dialysis equipment still requires comprehensive investigations regarding filter membrane materials, dialysate regeneration, long-term vascular access selection, treatment monitoring systems, and the remote guidance of medical care. Research and development in the field of wearable, regenerable, and portable artificial kidneys requires the cooperation of experts from multiple disciplines, such as medicine, materials science, bioengineering, mechanical engineering, and artificial intelligence. Regardless, improving patients' quality of life and reducing complications are common goals of clinicians and scientific researchers. Financial support and sponsorship This work was supported by Tsinghua University Initiative Scientific Research Program of Precision Medicine (Grant No. 2022TS007), Beijing Hospitals Authority Clinical medicine Development of special funding support (No. YGLX202332) and Capital' Funds for Health Improvement and Research (No. 2022-3-2243).
Yang et al. (Fri,) studied this question.