Many investigators have sought the development of an automated wearable artificial kidney (AWAK). Such a device would dramatically improve the quality of life of patients with end-stage renal disease (ESRD). They would live a relatively normal life, free of tiresome scheduled dialysis sessions, and no longer suffer from the ups and downs of body chemistry and the need for multiple medications. As with all forms of dialysis, the function of an AWAK is to cleanse the patient's blood of uremic waste metabolites, and to normalize fluid, electrolyte, and acid/base balance. In the native kidney, blood is filtered by passage through the glomerulus. The heart provides the energy for filtration. This function is readily duplicated in an AWAK by a battery-operated pump and hemofilter. The ultrafiltrate from the glomerulus is passed through the tubules, where it is modified by a host of secretory and absorption processes involving multiple enzymes requiring energy and specialized membranes. Duplicating the tubular function is a challenge that remains to be solved. One approach to an AWAK is to base it upon hemofiltration (HF). In HF, waste products are removed from the patient's blood by filtration and discarding the filtrate. The fluid (filtrate) and solutes discarded are replaced by intravenous infusion of replacement fluid. To meet the KDOQI guidelines of a weekly Kt/V of 2.0, a HF rate of 7 mL/min, 24 hours a day for 7 days a week would be required. This would result in a patient fluid loss of 420 mL/hr, or slightly more than 10 L/day. Replacing this loss would require at least 10 L of filtrate, which weighs 10 kg (22 pounds) and would not be wearable. In one clinically evaluated AWAK based upon HF, the fluid was replaced by having the patient drink 500 mL (about two 8 oz glasses) of dialysate every hour.1 The patient was able to do this for only 4 days. In addition, because of a loss of filtration capacity, the hemofilter was replaced every 2 days. With another clinically evaluated AWAK, the filtrate was regenerated using a custom-made miniature REDY sorbent cartridge.2 This was successful, except that the AWAK failed because the extracorporeal circuit clotted after 5 days. Another possible method of developing an AWAK would be to reclaim the water from the filtrate by reverse osmosis and then add a solute concentrate to prepare dialysate. However, as the solutes in the filtrate are concentrated, considerable pressure would be required, making this method unsafe to be worn. Developing an AWAK based upon hemodialysis would require the same methods as listed above. Major impediments to the development of an AWAK based upon methods requiring an extracorporeal circuit are interactions between the blood and extracorporeal circuit, both immunological and other reactions. Further, the circuit and patient must be anticoagulated. Even with adequate anticoagulation the extracorporeal circuit clots after several days.2 An anticoagulated patient could have internal hemorrhages, and there is the risk of external fatal bleeding resulting from an accidental disconnect. An AWAK based upon peritoneal dialysis requires no anticoagulant. In automated peritoneal dialysis (APD) 12–20 L of peritoneal dialysate per session are required. To develop an AWAK based upon APD, the amount of dialysate required could be reduced using the methods listed above. In continuous ambulatory peritoneal dialysis (CAPD) the peritoneal dialysate is stored in the abdomen for 4 hours, during which time the dialysate equilibrates with the patient's blood. During these 4-hour intervals the patient is relatively free to live a normal life. Thus, CAPD is a successful wearable artificial kidney but is not automated. Making dialysate exchanges every 4 hours for a lifetime can become tiresome. This is probably why the percentage of patients on CAPD in the U.S. has been decreasing each year relative to patients on APD. Another reason is that the total amount of dialysate that can be exchanged and the number of exchanges that can be made each day limits the efficiency of dialysis. Combining CAPD and APD using a sorbent cartridge to regenerate the dialysate can lead to the development of an AWAK, which is a significantly better modality than CAPD. The exchanges would be made continuously and automatically 24 hours a day, 7 days a week. At an average regenerated flow rate of 2 L/hour, the weekly urea Kt/V would be 3 times the KDOQI guidelines. Since the dialysate would be regenerated, there would be no need for additional dialysate, which would result in a waterless, bloodless AWAK. Further, the protein in the dialysate from the patient, which contains protein-bound toxins, could be regenerated and returned to the patient. For the first time, this would remove protein-bound toxins by dialysis. This is the approach we are taking toward the development of an AWAK.3
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Sep 28, 2007
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