Victor Gura

A wearable haemodialysis device for patients with end-stage renal failure: a pilot study

BACKGROUNDnMore frequent haemodialysis can improve both survival and quality of life of patients with chronic kidney disease. However, there is little capacity in the UK to allow patients to have more frequent haemodialysis treatments in hospital and satellite haemodialysis units. New means of delivering haemodialysis are therefore required. Our aim was to assess the safety and efficiency of a wearable haemodialysis device.nnnMETHODSnEight patients with end-stage kidney failure (five men, three women, mean age 51.7 [SD 13.8] years) who were established on regular haemodialysis were fitted with a wearable haemodialysis device for 4-8 h. Patients were given unfractionated heparin for anticoagulation, as they would be for standard haemodialysis.nnnFINDINGSnThere were no important cardiovascular changes and no adverse changes in serum electrolytes or acid-base balance. There was no evidence of clinically significant haemolysis in any patient. Mean blood flow was 58.6 (SD 11.7) mL/min, with a dialysate flow of 47.1 (7.8) mL/min. The mean plasma urea clearance rate was 22.7 (5.2) mL/min and the mean plasma creatinine clearance rate was 20.7 (4.8) mL/min. Clotting of the vascular access occurred in two patients when the dose of heparin was decreased and the partial thromboplastin time returned towards the normal reference range in both of these patients. The fistula needle became dislodged in one patient, but safety mechanisms prevented blood loss, the needle was replaced, and treatment continued.nnnINTERPRETATIONnThis wearable haemodialysis device shows promising safety and efficacy results, although further studies will be necessary to confirm these results.

Technical Breakthroughs in the Wearable Artificial Kidney (WAK)

BACKGROUNDnThe wearable artificial kidney (WAK) has been a holy grail in kidney failure for decades. Described herein are the breakthroughs that made possible the creation of the WAK V1.0 and its advanced versions V 1.1 and 1.2.nnnDESIGNnThe battery-powered WAK pump has a double channel pulsatile counter phase flow. This study clarifies the role of pulsatile blood and dialysate flow, a high-flux membrane with a larger surface area, and the optimization of the dialysate pH. Flows and clearances from the WAK pump were compared with conventional pumps and with gravity steady flow.nnnRESULTSnRaising dialysate pH to 7.4 increased adsorption of ammonia. Clearances were higher with pulsatile flow as compared with steady flow. The light WAK pump, geometrically suitable for wearability, delivered the same clearances as larger and heavier pumps that cannot be battery operated. Beta(2) microglobulin (beta(2)M) was removed from human blood in vitro. Activated charcoal adsorbed most beta(2)M in the dialysate. The WAK V1.0 delivered an effective creatinine clearance of 18.5 +/- 3.2 ml/min and the WAK V1.1 27.0 +/- 4.0 ml/min in uremic pigs.nnnCONCLUSIONSnHalf-cycle differences between blood and dialysate, alternating transmembrane pressures (TMP), higher amplitude pulsations, and a push-pull flow increased convective transport. This creates a yet undescribed type of hemodiafiltration. Further improvements were achieved with a larger surface area high-flux dialyzer and a higher dialysate pH. The data suggest that the WAK might be an efficient way of providing daily dialysis and optimizing end stage renal disease (ESRD) treatment.

Continuous Renal Replacement Therapy for End-Stage Renal Disease

Daily dialysis offers many benefits but is difficult to implement. CRRT allows dialysis 24/7 but is not suitable for ESRD patients. Thus, the need for a miniaturized ambulatory CRRT device those patients can wear permanently. We report the feasibility, safety and efficiency in uremic pigs, of such a wearable artificial kidney (WAK) that can be worn as a belt, operated with batteries, and weights less than 5 lbs. We used a hollow fiber dialyzer with a surface area of 0.2 sqm. Dialysate was continuously regenerated by a series of cartridges containing several sorbents allowing the use of approximately 375 ml of dialysate. The device includes reservoirs with heparin and electrolytes. Average fluid removal was 100 ml/hr. The Creatinine was 25 ml/min. In 8 hrs the total Creatinine removed was 1 gr, Urea 12 gr, P0.8 gr and K 72 mEq. Weekly st kt/v was extrapolated to approximately 7. There were no side effects. The WAK can be operated safely and continuously 168 hr/week. This would allow for all the advantages of daily dialysis and reduce morbidity and mortality in the ESRD population. It will also reduce cost and manpower utilization.

β2-Microglobulin and Phosphate Clearances Using a Wearable Artificial Kidney: A Pilot Study

BACKGROUNDnAdditional small-solute clearances during standard thrice-weekly hemodialysis treatments have not improved patient survival. However, these treatments have limited middle-molecule clearances. Thus, newer therapies designed to increase middle-molecule clearances need to be developed and evaluated.nnnSTUDY DESIGNnPilot clinical trial to measure beta(2)-microglobulin and phosphate clearances with a wearable hemodialysis device.nnnSETTING & PARTICIPANTSn8 regular hemodialysis patients under the care of a university teaching hospital.nnnINTERVENTIONnPatients were fitted with a wearable hemodialysis device for 4 to 8 hours.nnnOUTCOMESnAll patients tolerated the treatment.nnnRESULTSnAverage amount of beta(2)-microglobulin removed was 99.8 +/- 63.1 mg, with mean clearance of 11.3 +/- 2.3 mL/min, and an average of 445.2 +/- 326 mg of phosphate was removed, with mean plasma phosphate clearance of 21.7 +/- 4.5 mL/min. These clearances compared favorably with mean urea and creatinine plasma clearances (21.8 +/- 1.6 and 20.0 +/- 0.8 mL/min, respectively).nnnLIMITATIONSnProof-of-concept preliminary trial. Additional studies are warranted to confirm these positive preliminary data.nnnCONCLUSIONSnThis wearable artificial kidney potentially provides effective beta(2)-microglobulin and phosphate clearances and, by analogy, middle-molecule clearances.

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

Once hemodialysis had become established as a treatment for chronic kidney disease, the early pioneers realized the limitations of the treatment, particularly in terms of the impact intermittent thrice weekly hemodialysis had on a patient’s quality of life—not only time spent on dialysis and time traveling to and from treatment, but also dietary and fluid restrictions. This led to the search for the holy grail—a wearable hemodialysis device (WAK), that would allow patients to receive continuous treatment, while going on with the normal activities of daily life. Such a device would not only provide adequate solute clearances and control both electrolyte and acid–base status, but also improve blood pressure control—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 possible to construct a truly wearable device, which can accurately regulate ultrafiltration and achieve adequate solute clearances. One such device has recently completed successful human pilot studies, designed to test device reliability, safety, and efficacy.

Continuous renal replacement therapy for congestive heart failure: the wearable continuous ultrafiltration system.

Ultrafiltration is effective in the treatment of fluid and sodium overload in congestive heart failure. There is no available device to provide this therapy to ambulatory patients. We built and tested in vivo a wearable belt that can provide continuous ultrafiltration, 168 hours a week. Nine pigs underwent ureteral ligation and subsequently were allowed fluids ad lib, producing fluid overload. Next day, ultrafiltration was performed for 8 hours. The device consists of a hollow-fiber filter, a 9 V battery-operated pulsatile blood pump, a micro pump for heparin infusion, and another micro pump to control ultrafiltration rate. Blood flow was 65 ml/min and the weight of the device is less than 2.5 lb. Fluid removal rate ranged from 0 to 700 ml/h and averaged 106 ml/h. Salt removed was 7.6 g. No complications were observed. The potential impact on the quality of life of these patients by reducing the shortness of breath, leg swelling, and returning their ability to enjoy salt in their food might be significant, and a reduction in morbidity could be expected. The economic impact in reducing hospital admissions and length of stay, intensive care unit utilization, and drug consumption could be significant. Further studies are needed to compare this innovative approach with traditional drug-based therapy.

Ultrafiltration for the Management of Acute Decompensated Heart Failure

Heart failure is a major public health problem and is increasing in incidence throughout the industrialized world. Despite recent advances in pharmacotherapy, the overall mortality remains high and largely unchanged. Ultrafiltration has received increased attention in the treatment of acute decompensated congestive heart failure, and recent clinical trials suggest its usefulness in removing volume while preserving renal function. This review will focus on the background of ultrafiltration in the treatment of acute decompensated heart failure as well as the current evidence regarding its efficacy and safety.

A wearable artificial kidney for patients with end-stage renal disease

BACKGROUNDnStationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life.nnnMETHODSnWe conducted a FDA-approved human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable artificial kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours.nnnRESULTSnDuring the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 ± 24 ml/min, and mean dialysate flow was 43 ± 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 ± 10, 16 ± 8, and 15 ± 9 ml/min, respectively. Mean β2-microglobulin clearance was 5 ± 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows.nnnCONCLUSIONnTreatment with the wearable artificial kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable artificial kidney can be developed as a viable novel alternative dialysis technology.nnnTRIAL REGISTRATIONnClinicalTrials.gov NCT02280005.nnnFUNDINGnThe Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.

Portable and wearable dialysis: where are we now?

Although dialysis is a life‐saving treatment for patients with acute and chronic kidney disease, mortality remains high, with the survival of patients treated by regular hemodialysis similar to that of some solid organ tumors. Recent reports have suggested that a major increase in the dose of dialysis, delivered by frequent nocturnal dialysis, may improve survival. Unfortunately, only a minority of centers can offer this type of therapy, and only to a minority of their patients. Thus, to improve access to dialysis as well as increase the delivered dose of dialysis, a major change in the current paradigm of dialysis delivery is required. For many years, the “holy grail” of dialysis has been to develop a wearable or portable system, allowing patients to be treated while performing their normal activities of daily living. It is only recently with the advances in technology that such dialysis devices have been possible. Prototype devices for both hemodialysis and peritoneal dialysis have been studied with favorable results. Typically, these have been short‐term studies, and longer term trials are eagerly awaited, to determine whether the current generation of wearable continuous dialysis devices cannot only remove waste products of metabolism and control volume but also maintain acid‐base and electrolyte homeostasis and actually improve outcomes. In addition, a novel generation of dialysis devices based on nanotechnologies are being developed. Hopefully, these wearable continuous devices will be available as an option for routine clinical practice in the not‐too‐distant future.

Response to ‘A wearable hemofilter for continuous ambulatory ultrafiltration’

We thank Professors Shaldon and Lysaght1 for their insightful letter. The concept of developing wearable devices for treating both patients with heart failure and kidney failure is not new. The earliest attempt dates back to the work of Kolf et al.2 in the 1960s. Many nephrologists have subsequently tried to create a truly wearable device that would allow patients to carry out their normal daily living activities, or go to work, while being treated.