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The Wearable Artificial Kidney, Why and How: From Holy Grail to Reality

The Wearable Artificial Kidney, Why and How: From Holy Grail to Reality

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Published by: Mahmoud Diaa on Sep 10, 2011
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The Wearable Artificial Kidney, Why and How:From Holy Grail to Reality
Victor Gura,* Claudio Ronco,† and Andrew Davenport‡
*Cedars Sinai Medical Center, UCLA, The David Geffen School of Medicine, Los Angeles, California,†Department of Nephrology Dialysis & Transplantation, San Bortolo Hospital, Vicenza, Italy, and ‡UCL Centerfor Nephrology, Royal Free & University College Medical School, London, United Kingdom
ABSTRACT
Once hemodialysis had become established as a treatment forchronic kidney disease, the early pioneers realized the limita-tions of the treatment, particularly in terms of the impactintermittent thrice weekly hemodialysis had on a patient’squality of life—not only time spent on dialysis and time trav-eling to and from treatment, but also dietary and fluid restric-tions. This led to the search for the holy grail—a wearablehemodialysis device (WAK), that would allow patients toreceive continuous treatment, while going on with the normalactivities of daily life. Such a device would not only provideadequate solute clearances and control both electrolyteand acid–base status, but also improve blood pressure con-trol—all while allowing a liberal diet. Despite many attempts,to develop such a wearable artificial kidney, it is only recently,with the advent of microtechnologies, that it has been possi-ble to construct a truly wearable device, which can accuratelyregulate ultrafiltration and achieve adequate solute clear-ances. One such device has recently completed successfulhuman pilot studies, designed to test device reliability, safety,and efficacy.
Todayroutineoutpatientdialysisisnowregardedasawell-established technique, typically delivered in satellitedialysisunits,privateclinics,orminimalcarecenters,wellawayfromthe mainhospitalbase.However,inthe earlypioneering days, many obstacles had to be overcome,not only in the development of technology, but also theissues of reimbursement and patient eligibility. Besidesthe fundamental technological advances required todevelop dialyzers and dialysis machines (1), other keyadvanceswererequiredtomovetreatmentforwardfromits restrictive beginnings limited to patients with acutekidney injury, to the provision of chronic dialysis treat-ments. These included reliable vascular access (2) andheparinanticoagulationtopreventcircuitclotting.Once the early pioneers had conquered these majorhurdles and could deliver successful hemodialysis topatients with chronic kidney disease (CKD), they real-ized the limitations of the therapy, particularly its effectson patients’ lifestyle. As such, the search for a dialysisdevice that could be worn on a patient’s body can betracedbackseveraldecadestotheseearlypioneers(3–7).The main rationale for these attempts to attain wear-ability, were patient convenience and improved qualityoflife.These initial attempts to develop a WAK were ham-pered because of the need for large amounts of freshwater for dialysate, the size and weight of then availableblood and dialysate pumps, and the lack of portableenergy sources to power these pumps. Sorbents wereused to reduce the amount of fresh dialysate required,but the typical sorbent cartridge weight of over 2 kgreduced mobility. None of these devices could be com-mercially developed. Others created wearable hemo-filters (3), typically using arterial or arterio-venousaccess(5),buttoachieveadequatesoluteclearancesthenencountered the formidable obstacle of replacing largeamounts of ultrafiltrate effluent with suitable replace-ment solutions for intravenous infusion or oral replace-ment. While these techniques proved useful in the relief of fluid overload, they were not a commercially viablerenal replacement therapy (CRRT) for treating chronickidneyfailurepatients.Traditionally,hemodialysispatientshavebeenofferedthrice weekly hemodialysis. Over time, with furtheradvancesinmembranetechnology,dialysissessionscon-tinued thrice weekly but times were shortened from8 hours down to a worldwide average of 4 hours (8).However, shortening the dialysis session, with a com-pensatory increase in ultrafiltration rate, leads toincreased frequency of intradialytic hypotension (9, 10),
Address Correspondence to 
: Victor Gura, MD, AttendingPhysician. Cedars Sinai Medical Center, Associate ClinicalProfessor of Medicine. UCLA, The Geffen School of Medi-cine, 9100 Wilshire Blvd. Suite 360W, Beverly Hills, CA 90212,or e-mail: vgura@cs.com.Disclosures: Victor Gura is the Chief Medical Officer and adirector of Xcorporeal Inc.
Seminars in Dialysis 
—Vol 22, No 1 (January–February) 2009pp. 13–17DOI: 10.1111/j.1525-139X.2008.00507.x
ª
2008 Copyright the Authors.Journal compilation
ª
2008 Wiley Periodicals, Inc.13
 
with corresponding cardiac stunning. There is nowmounting evidence that increased dialysis frequency andprolonging dialysis sessions improve patient quality of life, and potentially increase life expectancy for CKDpatients (11–15). Increasing the duration of the dialysissession allows increased clearance of so called ‘‘middlemolecules,’’ and a slower, better tolerated rate of fluidremoval.Theemergingdataonthebenefitsofdailydial-ysisseemtoindicatethatfrequentandincrementaldialy-sis session time are key for improving the dismaloutcomeswecurrentlyachieveforCKDpatients.The concept that filtering blood for 9–12 hours
  ⁄  
weekcan restore the health of CKD patients back to that of anormal person, in whom the native kidneys filter blood24 hoursaday,7 daysaweek,appearssomewhatnaive.Furthercomplicatingthetimeissueisthephysicalchem-icalfactthatsolutesofdifferentsizetravelthroughdialy-sis membranes at different speeds, according to theirmolecular weight and charge. Thus, larger moleculesdiffuse slower, and may not adequately transit fromthe plasma water to the dialysate in the limited timeprovided.In addition, several uremic toxins [e.g.,
p
-cresol,reported to be associated with increased mortality (16)]are protein bound, and as such only a small amount isfree in plasma and available for removal. Time isrequired for protein bound toxins to re-equilibrate andraisetheplasmaleveloffreetoxin,andpermitadditionalremoval. Continuous removal of the free fraction wouldcreateagradientfromboundtofree fractionresultingintheeffectiveremovaloftoxins.Sorbentscanincreasetheremoval of these protein-bound toxins, such as
p
-cresol(17).It has also been shown that phosphate, an indepen-dent factor of all cause mortality in CKD patients, isonly efficiently removed when dialysis session time isextended (18). Therefore, it seems that more frequentand longer treatments may be far more physiologicalthan the current paradigm of 9–12 hours a week treat-ment.Theadvantagesofdailyextendeddialysisaresum-marizedinTable1.On the other hand, implementing more frequent andlonger, or daily dialysis programs is easier said thandone. There are major practical issues, including appro-priate manpower (nurses and technicians to supervisemore treatments in the dialysis units), building new dial-ysis facilities to cope with this expansion in dialysisrequirement, and the reluctance of governments andother payers to shoulder the expense of longer and morefrequent dialysis (19–22). In addition, patients may notwish to dialyze longer or more frequently and may beunableorunsuitabletodialyzeathome.Even if governments and payers would agree to payfortheadditionalcostsofdailydialysis,executingsuchataskwouldtaketime.Onealternativewouldbetominia-turize a dialysis machine and make it feasible for apatienttowearit.
Requirements for Continuous RenalReplacement Therapy
The various modes of continuous CRRT can deliversignificantly higher doses of dialysis, by treating patients24 hours a day, 7 days a week. However, CRRTmachines are not suitable to treat CKD patients, as theyrequire constant nursing time to treat a single patient. Inaddition, they are heavy, tethered to a wall electricaloutlet, and require large volumes of sterile replacementfluidordialysate(23).Whilsttreated,patientsareunableto mobilize and perform their activities of daily life. Aminiaturized and wearable CRRT machine (Fig. 1A)could potentially solve these problems. In order to buildaWAKthefollowingchallengeshadtobeovercome:
Power Source
Traditionalhemodialysis machines runonmains elec-tricity, with a back up heavy battery. So to be portable,a WAK must have a battery that, though small andlight, will provide enough energy to power all the neces-sary systems for a significant period of time to make theWAKindependentofafixedelectricaloutlet.
Dialysate
Standardhemodialysistherapyrequireslargevolumesof fresh dialysate. The volume of fresh dialysate wouldrequire a huge weight burden that would render wear-ability impossible. Thus, a WAK requires a sorbent sys-tem which can purify and regenerate effluent dialysate,so avoiding the need for fresh dialysate. In addition,thereisemergingevidencethatdialysateshouldbeultra-pure and free not only of bacteria but also of toxins andpyrogens. To provide such quality dialysate, the WAKuses sterile 0.45% saline in the dialysate circuit and boththetubingandsorbentsystemsaregammasterilized.
Additives
The final dialysate is made by adding an electrolytesolution and bicarbonate to the dialysis water, usinga proportionating system in the dialysis machine.
TABLE 1. The potential benefits of extended daily dialysis leadingto improved outcomes in the treatment of CKD patients
Improved soluteclearancesNo hyperkalemiaImproved appetite and nutritionLess bone disease and hyperparathyroidismEliminate the need for phosphate bindersImproved acid-base controlLess pruritusFewer sleep disturbancesReduced restless legsLess anemia and reduced ESA requirementImproved volumecontrolAppropriate sodium balanceImproved blood pressure controlDecreased use of anti hypertensive drugsReduced intradialytic hypotensionReduced risk of cardiac death and strokeImproved serumalbuminFewer cerebrovascular eventsLower expected morbidity and mortalityImproved sleeppatternsLess sleep apnea
14 Gura et al.
 
Similarly,theWAKwasdesignedtohavetwoadditionalpumps, one for a bicarbonate solution and a second foran electrolyte solution to be added to the dialysate com-partment(Fig.1B).
Fluid Removal
Standard hemodialysis machines allow controlledultrafiltration. Thus, the WAK must have a volumetricpump to remove fluid at a physiological rate to avoidhemodynamicproblemsandyetmaintaineuvolemia.
Ergonomic
For the WAK tobe truly portable for prolongedperi-ods, it has to be light and ergonomically adapted to thebody contour so that it can be worn continuously with-out impinging on the patient’s ability to sleep, ambulateorperformtheactivitiesofdailylife.
Pumps
Standard hemodialysis machines use large heavyroller pumps to propel blood and dialysate. A WAKbased on these pumps would be too heavy to be porta-ble. So a unique double channel pump was developed topropel both blood and dialsyate in opposite phase fortheWAK;itrequireslessenergythanthestandarddialy-sis machine roller pumps. The flow patterns generatedby this dual chamber pump differ from those of conven-tional blood pumps with an intermittent inversionof transmembrane pressures creating a ‘‘push pull’’mechanism that further improves convective transport.Push-pull mechanisms for increasing convective masstransport have been previously proposed, by using apiston pump to propel dialysate (24) but never commer-cially developed. The pump currently weighs 300 gramandisbatteryoperated.
Safety
Commercial dialysis machines are equipped withsafety systems to prevent passage of air to the patient,and to stop the blood pump in case of a disconnection.Thus,theWAKwasdevelopedtoincludeaservomecha-nism with a bubble detector sensor placed after theblood pump, designed to stop blood flow if air bubbleswere detected in the blood circuit, and a second servo-mechanism to halt the ultrafiltration pump if the bloodflow stopped for any reason. In addition, the pulsatilebloodpumphadaself-limitedcapacitytogeneratenega-tive pressure for suction from the arterial side of the vas-cular access, such that significant negative pressurescould not be applied to the vascular access. Thus, any
(A)(B)
Fig. 1.
(A) Photograph of WAK. (B) Circuit diagram of WAK.
THE WEARABLE ARTIFICIAL KIDNEY
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