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.

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.

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.

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.

Understanding safety-critical interactions with a home medical device through Distributed Cognition.

As healthcare shifts from the hospital to the home, it is becoming increasingly important to understand how patients interact with home medical devices, to inform the safe and patient-friendly design of these devices. Distributed Cognition (DCog) has been a useful theoretical framework for understanding situated interactions in the healthcare domain. However, it has not previously been applied to study interactions with home medical devices. In this study, DCog was applied to understand renal patients' interactions with Home Hemodialysis Technology (HHT), as an example of a home medical device. Data was gathered through ethnographic observations and interviews with 19 renal patients and interviews with seven professionals. Data was analyzed through the principles summarized in the Distributed Cognition for Teamwork methodology. In this paper we focus on the analysis of system activities, information flows, social structures, physical layouts, and artefacts. By explicitly considering different ways in which cognitive processes are distributed, the DCog approach helped to understand patients' interaction strategies, and pointed to design opportunities that could improve patients' experiences of using HHT. The findings highlight the need to design HHT taking into consideration likely scenarios of use in the home and of the broader home context. A setting such as home hemodialysis has the characteristics of a complex and safety-critical socio-technical system, and a DCog approach effectively helps to understand how safety is achieved or compromised in such a system.

Intensive Home Hemodialysis: An Eye at the Past Looking for the Hemodialysis of the Future.

Multiple observational studies along with a limited number of randomized clinical trials suggest that intensive hemodialysis (IHD) not only improves outcomes for uremic patients undergoing chronic dialysis but does so with a more favorable cost/benefit ratio compared with conventional hemodialysis. As a result of this, there has been a rapid increase in the interest in home hemodialysis (HHD) as HHD represents the easiest means of implementing IHD. While HHD has generated increased interest given its association with better outcomes/reduced hospitalizations, there are very few randomized controlled trials comparing HHD with other hemodialysis methods. Reported HHD-associated increased survival benefits compared with in-center hemodialysis are from uncontrolled studies, which raise patient selection bias as underlying the differences found. Thus, while HHD draws increasing attention, studies that pay careful attention to the psychosocial, demographic, and clinical factors associated with patients selected to undergo HHD will be needed to ultimately demonstrate its benefits, clarify the clinical applications, and determine the limits of IHD use in dialysis patients.

Patients' and carers' experiences of interacting with home haemodialysis technology: implications for quality and safety.

BACKGROUND: Little is known about patients' and carers' experiences of interacting with home haemodialysis (HHD) technology, in terms of user experience, how the design of the technology supports safety and fits with home use, and how the broader context of service provision impacts on patients' use of the technology. METHODS: Data were gathered through ethnographic observations and interviews with 19 patients and their carers associated with four different hospitals in the UK, using five different HHD machines. All patients were managing their condition successfully on HHD. Data were analysed qualitatively, focusing on themes of how individuals used the machines and how they managed their own safety. RESULTS: Findings are organised by three themes: learning to use the technology, usability of the technology, and managing safety during dialysis. Home patients want to live their lives fully, and value the freedom and autonomy that HHD gives them; they adapt use of the technology to their lives and their home context. They also consider the machines to be safe; nevertheless, most participants reported feeling scared and having to learn through mistakes in the early months of dialysing at home. Home care nurses and technicians provide invaluable support. Although participants reported on strategies for anticipating problems and keeping safe, perceived limitations of the technology and of the broader system of care led some to trade off safety against immediate quality of life. CONCLUSIONS: Enhancing the quality and safety of the patient experience in HHD involves designing technology and the broader system of care to take account of how individuals manage their dialysis in the home. Possible design improvements to enhance the quality and safety of the patient experience include features to help patients manage their dialysis (e.g. providing timely reminders of next steps) and features to support communication between families and professionals (e.g. through remote monitoring).

Home haemodialysis.

Haemodialysis (HD) began as an intensive care treatment offered to a very select number of patients in an attempt to keep them alive. Outcomes were extremely poor, and the procedure was cumbersome and labor intensive. With increasing expertise and advances in dialysis equipment, HD is now recognised as a life-sustaining treatment that is considered a standard of care for children with end stage renal disease (ESRD). Assessment of efficacy has evolved from mere survival, through achieving minimal standards of "adequate" dialysis with reduced morbidity, towards the provision of "optimal dialysis", which includes attempts to more closely mimic normal renal function, and of individualised care that maximizes the patient's health, psychosocial well-being and life potential. There is a renewed interest in dialysis, and the research profile has extended, exploring themes around convective versus diffusive treatments, HD time versus frequency and home versus in-centre dialysis. The results thus far have led dialysis care full circle from prolonged, home-based therapies to shorter, intense in-centre dialysis back to the belief that long or frequent HD at home achieves the best outcomes.

Medical technology at home: safety-related items in technical documentation.

OBJECTIVES: This study aimed to investigate the technical documentation of manufacturers on issues of safe use of their device in a home setting. METHODS: Three categories of equipment were selected: infusion pumps, ventilators, and dialysis systems. Risk analyses, instructions for use, labels, and post market surveillance procedures were requested from manufacturers. Additionally, they were asked to fill out a questionnaire on collection of field experience, on incidents, and training activities. RESULTS: Specific risks of device operation by lay users in a home setting were incompletely addressed in the risk analyses. A substantial number of user manuals were designed for professionals, rather than for patients or lay carers. Risk analyses and user information often showed incomplete coherence. Post market surveillance was mainly based on passive collection of field experiences. CONCLUSIONS: Manufacturers of infusion pumps, ventilators, and dialysis systems pay insufficient attention to the specific risks of use by lay persons in home settings. It is expected that this conclusion is also applicable for other medical equipment for treatment at home. Manufacturers of medical equipment for home use should pay more attention to use errors, lay use and home-specific risks in design, risk analysis, and user information. Field experiences should be collected more actively. Coherence between risk analysis and user information should be improved. Notified bodies should address these aspects in their assessment. User manuals issued by institutions supervising a specific home therapy should be drawn up in consultation with the manufacturer.

Exsanguination of a home hemodialysis patient as a result of misconnected blood-lines during the wash back procedure: a case report.

BACKGROUND: Home hemodialysis is common in New Zealand and associated with lower cost, improved survival and better patient experience. We present the case of a fully trained home hemodialysis patient who exsanguinated at home as a result of an incorrect wash back procedure. CASE PRESENTATION: The case involves a 67 year old male with a history of well controlled hypertension and impaired glucose tolerance. He commenced on peritoneal dialysis in 2006 following the development of end stage kidney failure secondary to focal segmental glomerulosclerosis. He transferred to hemodialysis due to peritoneal membrane failure in 2010, and successfully trained for home hemodialysis over a 20 week period. Following one month of uncomplicated dialysis at home, he was found deceased on his machine at home in the midst of dialysis. His death occurred during the wash back procedure performed using the "open circuit" method, and resulted from misconnection of the saline bag to the venous end of the extracorporeal blood circuit instead of the arterial end. This led to approximately 2.3L of his blood being pumped into the saline bag resulting in hypovolaemic shock and death from exsanguination. CONCLUSIONS: Despite successful training, critical procedural errors can still be made by patients on home hemodialysis. In this case, the error involved misconnection of the saline bag for wash back. This case should prompt providers of home hemodialysis to review their training protocols and manuals. Manufacturers of dialysis machinery should be encouraged to design machines specifically for home hemodialysis, and consider distinguishing the arterial and venous ends of the extracorporeal blood circuit with colour coding or incompatible connectivity, to prevent occurrences such as these in the future.

Self-care agency and perceived health among people using advanced medical technology at home.

AIM: This article reports a study of self-care agency and perceived health in a group of people using advanced medical technology at home. BACKGROUND: An increasing number of people are using medical technology for self-care. Few studies describe daily life in this context at an overriding level, irrespective of the specific sort of technology. A connection between self-care, perceived health and sense of coherence has previously been implied. METHODS: A descriptive, comparative, cross-sectional quantitative design was used. Data were collected from a questionnaire during the winter of 2009/2010. The questionnaire addressed perceived health and daily life with medical technology. Swedish versions of the Appraisal of Self-care Agency scale and the 13-item version of Antonovsky's sense of coherence scale were included. RESULTS: The questionnaire was answered by 180 adults performing self-care at home involving long-term oxygen, a ventilator, or peritoneal- or haemo-dialysis. Health-related and technology-related variables in daily life were mostly highly satisfactory. Perceived health was rated significantly lower among participants using long-term oxygen. Sufficient sense of coherence, knowledge of how to use technology, close contact with others and not feeling helpless contributed positively to self-care agency. Positive contributing factors for perceived health were being satisfied with life, having an active life and not feeling helpless, whereas age was a negative factor. CONCLUSION: Daily life is manageable for people in this context. Long-term oxygen treatment and advanced age can be regarded as risk factors for perceiving ill health.

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Mathematical analysis of the long-term efficacy of daily home hemodialysis therapy with a cold dialysate regeneration system.

BACKGROUND/AIM: We previously developed the cold dialysate regeneration system (CDRS) for use in daily home hemodialysis (HD). This study evaluates the long-term efficacy of the CDRS using a mathematical method. METHOD: HD with the CDRS was simulated using a method that integrates the mass-transfer model and the dialyzer solute kinetics model with a newly proposed model of CDRS function. RESULTS: We mathematically assessed the long-term efficacy of HD with the CDRS. The weekly treatment time required for HD with the CDRS was reduced significantly using the daily dialysis method; it required only an 11% longer treatment time to obtain the corrected equivalent renal clearance and a 14% shorter time for the standard Kt/V, compared with thrice weekly treatment with conventional HD. CONCLUSION: By developing a mathematical model to test the long-term efficacy of the new CDRS, we showed that HD with the CDRS is an efficient means of daily home hemodialysis therapy.

Review: understanding sorbent dialysis systems.

Although maintenance haemodialysis once had the benefit of two distinctly different dialysate preparation and delivery systems - (1) a pre-filtration and reverse osmosis water preparation plant linked to a single pass proportioning system and (2) a sorbent column dependent dialysate regeneration and recirculation system known as the REDY system - the first came to dominate the market and the second waned. By the early 1990s, the REDY had disappeared from clinical use. The REDY system had strengths. It was a small, mobile, portable and water-efficient, only 6 L of untreated water being required for each dialysis. In comparison, single pass systems are bulky, immobile and water (and power) voracious, typically needing 400-600 L/treatment of expensively pretreated water. A resurgence of interest in home haemodialysis - short and long, intermittent and daily - has provided impetus to redirect technological research into cost-competitive systems. Miniaturization, portability, flexibility, water-use efficiency and 'wearability' are ultimate goals. Sorbent systems are proving an integral component of this effort. In sorbent dialysate regeneration, rather than draining solute-rich dialyser effluent to waste - as do current systems - the effluent repetitively recirculates across a sorbent column capable of adsorption, ion exchange or catalytic conversion of all solute such that, at exit from the column, an ultra-pure water solution emerges. This then remixes with a known electrolyte concentrate for representation to the dialyser. As the same small water volume can recirculate, at least until column exhaustion, water source independence is assured. Many current technological developments in dialysis equipment are now focusing on sorbent-based dialysate circuitry. Although possibly déjà vu for some, it is timely for a brief review of sorbent chemistry and its application to dialysis systems.