A lifelong quest to make home hemodialysis simple, safe, and effective: A review of outcomes of 12 major projects.

In the course of over four decades, I have worked with an R&D team on 12 major R&D projects, all with the goal of making hemodialysis simple, safe, effective, and suitable for use in the home. Our team has worked within a University and in private companies and has collaborated with major healthcare drug and device companies. As a practicing nephrologist, my definition of success is when I see the device or drug we helped to develop in widespread clinical use. By this measure, two of the projects were highly successful, but seven failed. Most failures were due to decisions made by various corporations, governmental agencies, and venture capital groups, out of the hands or control of the R&D company. Three projects are still ongoing. There is no shortage of creativity or new ideas in nephrology and in dialysis. The major challenge is in the commercialization of the products.

Enhancement of solute clearance using pulsatile push-pull dialysate flow for the Quanta SC+: A novel clinic-to-home haemodialysis system.

BACKGROUND AND OBJECTIVE: The SC+ haemodialysis system developed by Quanta Dialysis Technologies is a small, easy-to-use dialysis system designed to improve patient access to self-care and home haemodialysis. A prototype variant of the standard SC+ device with a modified fluidic management system generating a pulsatile push-pull dialysate flow through the dialyser during use has been developed for evaluation. It was hypothesized that, as a consequence of the pulsatile push-pull flow through the dialyser, the boundary layers at the membrane surface would be disrupted, thereby enhancing solute transport across the membrane, modifying protein fouling and maintaining the surface area available for mass and fluid transport throughout the whole treatment, leading to solute transport (clearance) enhancement compared to normal haemodialysis (HD) operation. METHODS: The pumping action of the SC+ system was modified by altering the sequence and timings of the valves and pumps associated with the flow balancing chambers that push and pull dialysis fluid to and from the dialyser. Using this unique prototype device, solute clearance performance was assessed across a range of molecular weights in two related series of laboratory bench studies. The first measured dialysis fluid moving across the dialyser membrane using ultrasonic flowmeters to establish the validity of the approach; solute clearance was subsequently measured using fluorescently tagged dextran molecules as surrogates for uraemic toxins. The second study used human blood doped with uraemic toxins collected from the spent dialysate of dialysis patients to quantify solute transport. In both, the performance of the SC+ prototype was assessed alongside reference devices operating in HD and pre-dilution haemodiafiltration (HDF) modes. RESULTS: Initial testing with fluorescein-tagged dextran molecules (0.3 kDa, 4 kDa, 10 kDa and 20 kDa) established the validity of the experimental pulsatile push-pull operation in the SC+ system to enhance clearance and demonstrated a 10 to 15% improvement above the current HD mode used in clinic today. The magnitude of the observed enhancement compared favourably with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session) with the same dialyser and marker molecules. Additional testing using human blood indicated a comparable performance to pre-dilution HDF; however, in contrast with HDF, which demonstrated a gradual decrease in solute removal, the clearance values using the pulsatile push-pull method on the SC+ system were maintained over the entire duration of treatment. Overall albumin losses were not different. CONCLUSIONS: Results obtained using an experimental pulsatile push-pull dialysis flow configuration with an aqueous blood analogue and human blood ex vivo demonstrate an enhancement of solute transport across the dialyser membrane. The level of enhancement makes this approach comparable with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session). The observed enhancement of solute transport is attributed to the disruption of the boundary layers at the fluid-membrane interface which, when used with blood, minimizes protein fouling and maintains the surface area.

An immediate access dialysis graft designed to prevent needle-related complications: Results from the initial pre-clinical studies.

INTRODUCTION: No technology has been specifically developed with the intent to reduce needle-related vascular access injuries; a significant source of complications and abandonment. We present the initial pre-clinical study results of a novel, self-sealing, immediate cannulation dialysis graft that aims to prevent needle-related complications; to promote safe, reliable needle access; to reduce catheter use; and could facilitate home hemodialyisis. METHODS: The innovative graft design consists of two cannulation chambers with self-sealing properties and materials that prevent side and back wall needle puncture. Study and control grafts (expanded polytetrafluoroethylene) were implanted in one pig and 10 sheep in two studies over the course of 1 year. First cannulation occurred immediately post implant for all study grafts. Post-cannulation time to hemostasis, hematoma and seroma formation, infection, and patency were recorded. RESULTS: The two studies account for nearly 60 weeks (average 6.4 weeks/graft) of study graft follow-up. In the ovine study, average study graft time to hemostasis was 27.3 s (standard deviation = 26.3, range = 0-120), and the control averaged 177.2 s (standard deviation = 113.4, range = 60-600), p < 0.0001. Secondary patency was 75% and 67% for the study and control grafts, respectively. Neither study nor control groups experienced seroma, graft infections, or deaths. DISCUSSION: All novel grafts in the studies were implanted successfully and functioned as intended. There were no complications related to tunneling of the study graft and the chamber prevented back/side wall needle injury. This novel technology may help to mitigate these needle-related complications, while allowing for early/immediate cannulation which could also reduce catheter contact time.

Ambulatory Hemodialysis-Technology Landscape and Potential for Patient-Centered Treatment.

CKD is a worldwide health problem and the number of patients requiring kidney replacement therapy is rising. In the United States, most patients with ESKD rely on in-center hemodialysis, which is burdensome and does not provide the same long-term benefits as kidney transplantation. Intensive hemodialysis treatments have demonstrated improved clinical outcomes, but its wider adoption is limited by equipment complexity and patient apprehension. Ambulatory devices for hemodialysis offer the potential for self-care treatment outside the clinical setting as well as frequent and prolonged sessions. This article explains the motivation for ambulatory hemodialysis and provides an overview of the necessary features of key technologies that will be the basis for new wearable and implantable devices. Early work by pioneers of hemodialysis is described followed by recent experience using a wearable unit on patients. Finally, ongoing efforts to develop an implantable device for kidney replacement and its potential for implantable hemodialysis are presented.

Biochemical comparison of 8 h haemodialysis and 4 h haemodiafiltration, and two dialysis membranes, in a randomized cross-over trial.

AIM: Extended-hours haemodialysis has long been regarded as the optimal form of dialysis for solute clearance. With emerging benefits of haemodiafiltration, we wanted to compare these two head-to-head. METHODS: In this randomized cross-over trial, we recruited existing nocturnal haemodialysis patients, who had not been hospitalized in the prior 3 months. After a baseline 8 h haemodialysis session, subjects were randomized to either 2 weeks of 8 h haemodialysis or 4 h haemodiafiltration with cross-over to the alternative treatment after a 2-week washout period. Subjects were additionally randomized to the Fresenius FX80 or Nipro Elisio in a parallel design. Blood and dialysate samples were collected at baseline and at the end of both study periods. RESULTS: Twelve patients completed the study. Mean (SD) age and body mass index were 55.1 ± 11.5 years and 36.4 ± 10.8, respectively. Urea and creatinine reduction ratios were higher with extended-hours haemodialysis compared to haemodiafiltration (difference 14.0%, 95% CI = 10.6, 17.3; P < 0.001 and 9.1%, 95% CI = 11.0, 7.2; P < 0.001). Fibroblast growth factor 23 (FGF23) clearance was superior with haemodiafiltration (difference 20.1%, 95% CI = 8.7, 31.6; P = 0.001). No difference was seen in reduction ratios for phosphate, retinol binding protein, alpha-1-microglobulin, beta-2-microglobulin and fetuin with both modalities. Compared to Nipro Elisio, Fresenius FX80 dialyser achieved higher beta-2-microglobulin clearance (Period 1: difference 7.8%, 95% CI = 1.3, 14.4; P = 0.02, Period 2:7.5%, 95% CI = 1.0, 14.1; P = 0.02). CONCLUSIONS: Small solute clearance was superior with extended-hours haemodialysis while haemodiafiltration enhanced FGF23 clearance. Beta-2-microglobulin clearance was improved with Fresenius FX80 dialyser, but this difference is unlikely to be clinically significant.

Haemodialysis at home: review of current dialysis machines.

INTRODUCTION: Only a minority of patients with chronic kidney disease treated by hemodialysis are currently treated at home. Until relatively recently, the only type of hemodialysis machine available for these patients was a slightly smaller version of the standard machines used for in-center dialysis treatments. AREAS COVERED: There are now an alternative generation of dialysis machines specifically designed for home hemodialysis. The home dialysis patient wants a smaller machine, which is intuitive to use, easy to trouble shoot, robust and reliable, quick to setup and put away, requiring minimal waste disposal. The machines designed for home dialysis have some similarities in terms of touch-screen patient interfaces, and using pre-prepared cartridges to speed up setting up the machine. On the other hand, they differ in terms of whether they use slower or standard dialysate flows, prepare batches of dialysis fluid, require separate water purification equipment, or whether this is integrated, or use pre-prepared sterile bags of dialysis fluid. EXPERT COMMENTARY: Dialysis machine complexity is one of the hurdles reducing the number of patients opting for home hemodialysis and the introduction of the newer generation of dialysis machines designed for ease of use will hopefully increase the number of patients opting for home hemodialysis.

How an ordeal becomes the norm: A qualitative exploration of experiences of self-cannulation in male home haemodialysis patients.

OBJECTIVES: Despite home haemodialysis (HHD) being associated with significant health and psychosocial benefits, it remains an under-utilized dialysis modality for people with chronic kidney disease. Self-cannulation, where patients insert their own needles for dialysis, is a key component of HHD. Recent research suggests that the prospect of self-cannulation is a barrier for patients, but there is little research which examines why this is the case. The aim of this study was to explore male HHD patients' experiences and attitudes towards self-cannulation. DESIGN: Qualitative methods were adopted to gather in-depth views from experienced HHD patients from a UK renal centre. METHODS: Semi-structured interviews were conducted with eight male HHD patients (HHD duration: 12-55 months). During the interview, the researcher elicited participants' lived experience of self-cannulation. Topics included the decision to self-cannulate and the impact of self-cannulation on the patient. The data collected were analysed using interpretative phenomenological analysis. RESULTS: The findings from this study elucidate the process of how self-cannulation changed from an ordeal to the norm in these participants' lives. The central theme from these interviews is that 'becoming a person who self-cannulates is a process'. Three super-ordinate themes were discussed that relate to this central theme: 'gaining control', 'building confidence', and 'becoming the norm'. CONCLUSIONS: The findings from this study suggest that some patients' initial fears of self-cannulation can be overcome. These findings offer health care professionals and patients alike a greater understanding of how patients who self-cannulate conceptualize it and its role in their mental and physical health. Statement of contribution What is already known on this subject? Home haemodialysis is a cost-effective form of renal replacement therapy which is under-utilized in the United Kingdom. Home haemodialysis is associated with positive health outcomes. Self-cannulation is noted as a barrier to home haemodialysis. What does this study add? Describes the process by which male dialysis patients became proficient in self-cannulation. Highlights psychological mechanisms which may facilitate and maintain self-cannulation. Suggests practical techniques which can be incorporated into renal clinics and care plans.

[Home Daily Hemodialysis with NxStage System One: monocentric italian casistic results]. / Dialisi domiciliare quotidiana con Nxstage System One: analisi dei risultati in una casistica monocentrica italiana.

NxStage System One is a new dialytic technology based on easy setup, simplicity of use and reduced dimensions, which is increasingly in use worldwide for home hemodialysis treatments. The system utilizes a low amount of dialysate, usually 15-30 liters according to anthropometric patients' values. The dialysate is supplied at very low flux, generally about 1/3 of blood flow, in order to obtain an elevated saturation of dialysate for solutes. In these conditions the clearance of urea will be almost equal to dialysate flow rate. In order to achieve an obptimal weekly clearance evaluated by Std Kt/V the dialysis sessions are repeated six times a week. In this way a good control of blood voleme can be reached. In this paper we report our experience of treatment with NxStage System One in 12 patients from May 2011 to Dicember 2016.

[Low flux dialysate daily home hemodialysis: A result for the 62 first French and Belgian patients]. / Hémodialyse quotidienne à bas débit de dialysat à domicile : résultats cliniques et biologiques des 62 premiers patients traités en France et en Belgique.

Since 2011, a new device is available for low flux dialysate quotidian home hemodialysis in France and Belgium. This study aims to evaluate the characteristics and dialysis prescriptions for Nx Stage System One™ users. We retrospectively included patients trained between 2011 and 2013 in France and Belgium. We collected data concerning their clinical features, their dialysis prescriptions, their laboratory parameters until 6 months of dialysis and, reason for dropping in case of cessation. Sixty-two patients from 31 centers, aged 48±18 years old, with a sex ratio 46/16 (M/F) are included with a median Charlson comorbidity index of 1 [0-3]. Of these patients, 71% are anuric and have been on dialysis for a mean time of 136.6±125 months. Previously, most of them had been taken care of in satellite units of dialysis (45%) and 14% are incident patients. In total, A total of 60% have an arterio-veinous fistula (AVF), with 18 patients using the Buttonhole system and 2 patients have a tunneled catheter. Median time for training was 26.5 days (17-45). Among the patients, 69% are dialyzed 6 days a week, during a mean time of 142.5±20 minutes with a volume of 20.9±3 liters of dialysate and without anticoagulant (63%). Predialytic levels of hemoglobin, creatinin, urea, phosphorus and ß2microglobulin remain stable. On the contrary, there is a significant improvement of albumin and bicarbonate levels. Technique survival was 75% at 1 year, and major reason for cessation was kidney transplant. It seems that this device fits for young patients, with few comorbidities and a long past in renal chronic failure. These results suggest that dialysis adequacy is acceptable despite low dialysate volumes but need confirmation with a longer follow up and a larger cohort.

Clinical safety and performance of VIVIA: a novel home hemodialysis system.

Background: The VIVIA Hemodialysis System (Baxter Healthcare Corporation, Deerfield, IL, USA) was designed for patient use at home to reduce the burden of treatment and improve patient safety. It has unique features including extended use of the dialyzer and blood set through in situ hot-water disinfection between treatments; generation of on-line infusible-quality dialysate for automated priming, rinseback and hemodynamic support during hypotension and a fully integrated access disconnect sensor. Methods: The safety and performance of VIVIA were assessed in two clinical studies. A first-in-man study was a prospective, single-arm study that involved 22 prevalent hemodialysis (HD) patients who were treated for ∼4 h, four times a week, for 10 weeks. A second clinical study was a prospective, single-arm study (6-8 h of dialysis treatment at night three times a week) that involved 17 prevalent patients treated for 6 weeks. Results: There were 1114 treatments from the two studies (first-in-man study, 816; extended duration study, 298). Adverse events (AEs) were similar in the two studies to those expected for prevalent HD patients. No deaths and no device-related serious AEs occurred. Adequacy of dialysis ( Kt / V ) urea in both clinical trials was well above the clinical guidelines. VIVIA performed ultrafiltration accurately as prescribed in the two studies. The majority of patients achieved 10 or more uses of the dialyzer. Endotoxin levels and bacterial dialysate sampling met infusible-quality dialysate standards. Conclusion: These results confirm the safety and expected performance of VIVIA.

[The history of home hemodialysis and its likely revival]. / Storia dell'emodialisi domiciliare e della sua probabile rinascita.

The home extracorporeal hemodialysis, which aroused a great interest in the past, has not kept its promises due to the complexity and expectations for family involvement in treatment management. In the United States NxStage One portable system was proposed and designed for home use. In this work we describe, starting from the history of home hemodialysis, the method with NxStage system by comparing it with the conventional HD in 5 patients. The dialysis efficiency was similar between the two treatments, even if home hemodialysis showed a reduction in serum urea, creatinine and phosphorus. At the same time phosphate binders use decreased with an increase in serum calcium while hemoglobin increased reducing doses of erythropoietin. The method was successful in the training of the patients and their partners during hospital training and at home. Patients have shown great enthusiasm at the beginning and during the therapy, which is developed around the users personal needs, being able to decide at its own times during 24 hours according to personal needs, in addition to faster recovery after the dialysis. This method certainly improved the patients' wellness and increased their autonomy.

Home hemodialysis in children.

Pediatric home hemodialysis is infrequently performed despite a growing need globally among patients with end-stage renal disease who do not have immediate access to a kidney transplant. In this review, we expand the scope of the Implementing Hemodialysis in the Home website and associated supplement published previously in Hemodialysis International and offer information tailored to the pediatric population. We describe the experience and outcomes of centers managing pediatric patients, and offer recommendations and practical tools to assist clinicians in providing quotidian dialysis for children, including infrastructural and staffing needs, equipment and prescriptions, and patient selection and training.

NxStage dialysis system-associated thrombocytopenia: a report of two cases.

Thrombocytopenia in hemodialysis patients has recently been reported to be commonly caused by electron-beam sterilization of dialysis filters. We report the occurrence of thrombocytopenia in the first two patients of a newly established home hemodialysis program. The 2 patients switched from conventional hemodialysis using polysulfone electron-beam sterilized dialyzers to a NxStage system, which uses gamma sterilized polyehersulfone dialyzers incorporated into a drop-in cartridge. The thrombocytopenia resolved after return to conventional dialysis in both patients and recurred upon rechallenge in the patient who opted to retry NxStage. This is the first report of thrombocytopenia with the NxStage system according to the authors’ knowledge. Dialysis-associated thrombocytopenia pathophysiology and clinical significance are not well understood and warrant additional investigations.

A Comparison of Clinical Parameters and Outcomes over 1 Year in Home Hemodialysis Patients Using 2008K@home or NxStage System One.

The prevalence of home hemodialysis (HHD) in the United States is growing, driven in part by improvements in dialysis machines for home use. We assessed clinical parameters and outcomes in HHD patients using either Fresenius 2008K@home or NxStage System One over 1 year. Patients were 18 years or older and received HHD for ≥30 days between January 1, 2009, and June 30, 2010. A propensity score match was used to control for differences in baseline characteristics, and 2008K@home patients were stratified by frequency of use. Data for outcome measures were analyzed using generalized linear mixed models. Treatment frequency was lower for 2008K@home groups than System One. Mean standardized Kt/V (stdKt/V) was 2.75 for 2008K@home ≥3.5x/week users and 1.99 for System One users (p < 0.001). Erythropoiesis-stimulating agent use tended to be lower for patients using System One. There were no statistically significant differences across groups in serum albumin, calcium, phosphorus, hemoglobin, or parathyroid hormone levels, normalized protein catabolic rate, body mass index, number of hospitalizations, or hospitalized days. Clinical parameters and outcomes for HHD patients using 2008K@home and System One were largely equivalent, although 2008K@home use was associated with higher stdKt/V. Further studies will be required to establish whether these differences in stdKt/V relate to differences in technology, treatment schedule, or a combination thereof.