Andrew Davenport

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

BACKGROUND More 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. METHODS Eight 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. FINDINGS There 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. INTERPRETATION This wearable haemodialysis device shows promising safety and efficacy results, although further studies will be necessary to confirm these results.

Audit of the Effect of Dialysate Sodium Concentration on Inter-Dialytic Weight Gains and Blood Pressure Control in Chronic Haemodialysis Patients

Background/Aims: Over the last three decades the standard dialysate sodium concentration has increased from 136 to 140 mmol/l (mEq/l) today. There has been great debate as to whether a reduction in dialysate sodium alone can lead to improved blood pressure control, and reduced inter-dialytic weight gain. Methods: An audit was performed in 469 maintenance regular haemodialysis patients who dialysed in seven different centres under the care of one university medical school. Results: Those centres which predominantly used a dialysate sodium of 140 mmol/l (mEq/l) had increased inter-dialytic weight gains, with more difficult blood pressure control, as not only did a greater percentage of patients require anti-hypertensive medication, but also more were prescribed multiple classes of anti-hypertensive agents. There was no difference in the frequency of symptomatic intra-dialytic hypotension. Conclusions: A reduction in dialysate sodium was associated with lower inter-dialytic weight gains, without any additional intra-dialytic hypotensive episodes. Those patients in whom the difference between the time-averaged dialysate sodium concentration and the midweek pre-dialysis serum sodium was positive result had increased inter-dialytic weight gains, compared to those with a negative value. Reduced dialysate sodium alone was not effective in controlling blood pressure without additional proper dietary sodium restriction.

More dietetic time, better outcome?

Background/Aim: A randomized controlled trial was conducted involving 67 stable adult haemodialysis patients with hyperphosphataemia. The objective was to determine the effect of monthly dietetic consultations on patients’ serum phosphate concentrations and calcium × phosphate product. Methods: The intervention group received monthly dietetic consultations for 6 months using advanced counselling skills aimed at limiting phosphate intake in the diet and improving compliance with phosphate binders, whereas standard care with dietetic consultations every 6 months was provided to the control group. Results: Serum phosphate concentrations decreased in the intervention group from 2.05 ± 0.48 to 1.80 ± 0.48 mmol/l by month 3 (p < 0.05). However, this subsequently increased and by month 6 there was no significant difference from baseline. After controlling for confounding variables, the difference between the groups was approaching significance at month 3, but there was no difference by month 6, or following conclusion of the study. The calcium × phosphate product similarly decreased in both groups, achieving K/DOQI standards, but was not sustained either during the remainder of the study but decreased further by the 12-month follow-up and, although it was not significantly different, it did improve significantly from baseline in both the intervention and control groups. Conclusion: Increased frequency of dietetic consultations can result in improved phosphate control in the short term, and therefore more innovative strategies appear necessary to sustain longer-term control.

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

BACKGROUND Additional 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. STUDY DESIGN Pilot clinical trial to measure beta(2)-microglobulin and phosphate clearances with a wearable hemodialysis device. SETTING & PARTICIPANTS 8 regular hemodialysis patients under the care of a university teaching hospital. INTERVENTION Patients were fitted with a wearable hemodialysis device for 4 to 8 hours. OUTCOMES All patients tolerated the treatment. RESULTS Average 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). LIMITATIONS Proof-of-concept preliminary trial. Additional studies are warranted to confirm these positive preliminary data. CONCLUSIONS This wearable artificial kidney potentially provides effective beta(2)-microglobulin and phosphate clearances and, by analogy, middle-molecule clearances.

Ultrafiltration in Diuretic-Resistant Volume Overload in Nephrotic Syndrome and Patients with Ascites due to Chronic Liver Disease

Patients with nephrotic syndrome and those with cirrhosis are predisposed to salt and water retention due to reduced renal sodium excretion. Despite the prescription of low-sodium diets and diuretics, some patients develop refractory oedema. When other medical treatments have been ineffective, isolated ultrafiltration and hemofiltration have been successfully used to treat refractory nephrotic patients. Following fluid removal, patients become responsive to diuretics. In cirrhotic patients, re-infusion of ascites and paracentesis with albumin infusion have been reported to be equally effective in managing ascites refractory to diuretic and other standard therapies. Although isolated ultrafiltration has not been successful in controlling ascitic fluid, hemofiltration has been shown to be beneficial, whereas standard intermittent hemodialysis has been reported to be ineffective.

Artificial hepatic support - Where are we now?

The advent of successful orthotopic liver transplantation for patients with both acute and chronic liver failure has been a major breakthrough in clinical practice, for patients who would have otherwise died [1]. Patients with chronic liver disease are now listed for transplantation well before terminal liver failure, and therefore can potentially wait for a suitable donor liver. However, those with acute hepatic failure [2] can be desperately ill, and may require urgent transplantation. Unfortunately, the number of patients with liver disease awaiting transplantation now exceeds the donation rate. If no liver is immediately available, and the clinical condition of the patient is deteriorating, then the question of artificial liver support arises. Similarly, some patients will have contraindications to transplantation, due to cardiovascular or intracranial instability, sepsis or psychosocial factors [3]. In these cases artificial liver support may help, and so allow subsequent transplantation. Patients with chronic liver disease may develop encephalopathy and hepatorenal syndrome [4] secondary to acute events including sepsis and gastrointestinal hemorrhage. Artificial liver support may help to quicken recovery from such acute events. Over the years several treatments have been advocated to improve survival in both patients with acute and chronic liver failure. After initial success reported in small selected series, many have not then been substantiated in larger randomized controlled trials. Dialysis

Anticoagulation Options for Pediatric Hemodialysis

Blood coagulation in the extracorporeal hemodialysis circuit is one of the manifestations of bio‐incompatibility that is related to the activation of monocytes, platelets, and the coagulation cascades. Compared to adults, in pediatric patients, the surface area of the extracorporeal circuit is increased relative to blood volume. This is due to the patients smaller blood volume and the combination of the higher relative surface area of the dialyzer, smaller lumen lines, and small‐bore vascular catheters, potentially increasing contact activation of coagulation proteins, platelets, and inflammatory cells. Although unfractionated heparin remains the most commonly used anticoagulant, low molecular weight heparin offers the advantages of a single bolus, less fibrin and platelet deposition in the dialyzer, and perhaps more importantly, less osteoporosis, hyperkalemia, and abnormal lipoprotein profile. Although regional anticoagulants are available, these are often prohibitively expensive or require increased complexity of the dialysis procedure (e.g., citrate), but have the advantage of reducing the risk of bleeding when compared to heparin. Thrombin inhibitors are now available, and with the advent of argatroban, which is metabolized in the liver, have become the anticoagulants of choice for the few patients who develop heparin‐induced thrombocytopenia type II.

Continuous Renal Replacement Therapy for Liver Disease

Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for critically ill patients with acute renal failure around the world. In particular, CRRT is used for patients with combined liver and acute renal failure, because they are often hemodynamically unstable. The question arises as to whether the use of CRRT should be extended to those patients with acute and chronic liver failure who do not have dialysis‐dependent renal failure. CRRT could potentially allow some detoxification by removing water‐soluble toxins and also allow regulation of intravascular volume and correction of sodium and other electrolyte and acid–base imbalances. By providing homeostatic control, CCRT could potentially help support patients by bridging to liver transplantation and managing those who eventually recover with hepatic regeneration.

Extracorporeal Support for Patients with Hepatic Failure

Extracorporeal support has been advocated for patients with acute and chronic liver failure. Patients with acute liver failure and those with decompensated cirrhosis can be broadly divided into two groups. The first group comprises those with acute liver failure and ongoing hepatic necrosis, and the second, those with long‐standing chronic decompensation admitted with one or more complications of liver failure, such as encephalopathy without any evidence of a precipitating factor or accompanying acute deterioration of liver function. This second group includes patients with acute liver failure, where the insult causing hepatic necrosis has been resolved, and those patients with chronic decompensation who suffer another insult to the liver, such as acute infection or variceal hemorrhage that causes further liver injury in the setting of multiorgan failure. These two groups are likely to have different outcomes and may need to be managed differently. In the first group, liver transplantation is the only possible long‐term therapeutic option, whereas in the second group, other possibilities such as extracorporeal liver support systems and/or medical therapy may allow these patients to return to their previous state before the acute insult. Over time extracorporeal support has expanded from simple peritoneal dialysis and hemodialysis, to the development of circuits designed primarily to remove both water and lipid‐soluble toxins and, in addition, bioartificial devices to provide replacement synthetic hepatic function.

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.