When patients with chronic kidney disease (CKD) progress to end-stage renal disease (ESRD), and the glomerular filtration rate (GFR) is less than 10ml/1.73㎡, renal replacement therapy (KRT) must be considered. Currently, the most effective KRT is kidney transplant . However, in addition to donor kidney shortage, patients must also receive immunosuppressive treatment. Therefore, many patients with ESRD cannot receive kidney transplant treatment.
In view of the above situation, many ESRD patients have received other KRT therapies, such as blood or peritoneal dialysis , but these KRTs have many problems, such as hemodialysis 3/4 times a week will have a huge impact on the patient's work and life. Therefore, the American Society of Nephrology (ASN), the U.S. Food and Drug Administration (FDA), and some patient organizations have called for disruptive KRTs, such as portable dialysis devices (WAKs) and even implantable artificial kidneys. Disruptive KRT will benefit the patient's work, life and mental state, further improving the patient's final prognosis.
On September 21, 2022, Artificial Organs released a review from American experts, which summarizes the current research and clinical application status of WAK and artificial kidneys. It is reported that some WAKs have been used in clinical research, and prototypes of artificial kidneys have also been released. The review divides the novel KRT technology into WAK, in vitro biological artificial renal system (BAK), in vivo artificial kidney and other methods. This article will mainly introduce portable dialysis machines for readers. Compared with hemodialysis, peritoneal dialysis does not require blood pathways, and the amount of dialysis fluid is used lower than that of hemodialysis. In view of this, peritoneal dialysis technology is more suitable for portable dialysis machines than hemodialysis. In addition, portable peritoneal dialysis may be safer than portable hemodialysis operations.
At present, 4 portable peritoneal dialysis machines and 1 portable hemodialysis machine have been released. See Table 1 for details.
Table 1 Summary of portable dialysis machines
ViWAK is a portable peritoneal dialysis machine that performs continuous peritoneal dialysis through a dual-cabin peritoneal catheter and a small battery-driven rotary pump. The ViWAK system uses polystyrene resin and activated carbon to adsorb toxins in the blood. During daytime dialysis, 2L of standard glucose-based dialysate is injected into peritoneal cavity , and 2L is left. The dialysate can be recycled for 10 hours. After the day dialysis was completed, all dialysate was discharged and 2L acodextrin dialysate was used for night dialysis. However, ViWAK lacks a selective uremia toxin removal system and cannot correct electrolyte changes. Although in vitro studies have shown that ViWAK can remove creatinine and middle molecules, due to its limitations, there are currently no animal or human research reports.
AWAK is another portable peritoneal dialysis machine. Compared with ViWAK, AWAK is a single cavity peritoneal dialysis machine. The dialysis process is to inject standard glucose dialysate into the patient's peritoneal cavity and dialyze it in a 4L/h interval dialysate recirculation method, with an equivalent dialysis volume of 96L/d. In order to reduce dialysis water and reduce the quality of the whole machine, AWAK adopts improved cyclic dialysis adsorption technology (REDY). REDY monitors changes in uremia toxins and electrolytes and can regulate electrolytes. After REDY is applied, the dialysate of AWAK only needs to be replaced once every 1 month, but the adsorbent kit needs to be replaced once every 4 to 8 hours. At present, animal and human studies have shown that AWAK ultrafiltration urea, creatinine and phosphorus have better effects, which is comparable to conventional peritoneal , but more than half of the patients complain of abdominal discomfort after dialysate drainage. Currently, AWAK's commercial applications are under development.
WEAKID project is a research conducted by the EU scientific team in the Netherlands, aiming to make commercially available portable dialysis machines. The WEAKID project has two dialysis systems, namely ① large-capacity night therapy device; ② small-volume daytime continuous therapy device. Like AWAK, it adopts a batch dialysis mode and has an adsorption box. The adsorption box needs to be replaced twice a day and contains activated carbon and ion exchanger . WEAKID does not use standard glucose dialysate. Its dialysate has less glucose , but because it does not have static residence, it retains a high osmosis gradient, allowing WEAKID to be ultrafiltration efficiently. At the same time, due to the reduction of glucose concentration, the peritoneal deterioration can be prevented and the time for peritoneal dialysis can be increased.In vitro studies have confirmed that WEAKID can remove potassium, phosphorus, urea and creatinine, and its efficiency is better than ordinary peritoneal dialysis. A study based on a pig model of uremia confirmed that clearance rates of creatinine and phosphorus were 2 times and 1.6 times respectively.
CLS is a portable peritoneal dialysis machine designed by Swedish company Triomed AB. During the initial use of CLS, 2L dialysate is required to inject into the peritoneal cavity of the patient. CLS's peritoneal dialysate can be continuously recycled, but the adsorption box needs to be replaced every 4 hours. In clinical studies, CLS and automated peritoneal dialysis have the same efficiency in urea, creatinine and phosphate clearance. In addition, during dialysis, the glucose concentration of intraperitoneal dialysate in the CLS group was stable, which achieved long-term high-efficiency ultrafiltration, and no adverse events of or patient discomfort were observed.
Currently, the Gura team has developed a portable hemodialysis machine with dialysate regeneration function. The dialysis machine consists of a wearable hemodialysis device and a battery-powered dialysis pump. Similar to conventional hemodialysis, a dialysis pump pumps heparinized blood into a dialysis machine. In a portable hemodialysis machine, the waste liquid decomposes the urea through a chamber containing urea enzyme; the phosphate in the waste liquid can be adsorbed and purified through a chamber containing zirconium phosphate and hydrated zirconium oxide; and through the activated carbon chamber, other compounds can be adsorbed and purified. After the above steps, the waste liquid will be changed into a dialysate again, which is the dialysate regeneration function, which will greatly reduce the amount of dialysate. At present, the FDA has approved the relevant clinical trials of the device. The results of the trial showed that the five patients had better clearance of urea, creatinine, phosphate and β2 microglobulin, which may be the dawn of a portable hemodialysis device.
3 of the above five portable dialysis devices have entered the clinical research stage and have achieved some results. This may mean that in the near future, ESRD patients only need a "waist pack" or "backpack" to return to society, work and family, and can also enjoy traveling as they say and go.
References:
1. Groth T, Stegmayr BG, Ash SR, et al. Wearable and implantable artistic kidney devices for end-stage kidney disease treatment-Current status and review. Artif Organs. 2022 Sep 21.
