The innovative dialysis devices requiring real-time monitoring of alarms, dialysis parameters, and patient-related data may be possible only with incorporation of AI.
Acute and chronic dialysis therapies have evolved from a primordial and artisanal stage into a high-tech procedure with dedicated biomaterials and new devices. A great part of the scientific evolution is concerned with the specific information and communication technology applied to dialysis machines. The rapid changes in the patient during treatment and the inter-individual variability of clinical requirements have spurred new interest in the application of precision medicine to this area. In particular, after an initial development of manual, semi-automatic, or fully automatic biofeedback control in chronic hemodialysis, this approach is now turning into reality in the area of critical care nephrology and acute dialysis in the context of continuous renal replacement therapy (CRRT). The complexity of the critically ill patients with acute kidney injury and other comorbidities requires a rapidly changing prescription modality followed by an immediate feedback from the machine. Signals from the patient, laboratory medicine, and the extracorporeal circuit are integrated in a multi-input/multi-output expert system that makes immediate and accurate changes in treatment delivery by the machine. The feedback can be either authorized by the operator or directly executed by the machine without human intervention. The machine can automatically modify treatment time, dialysate composition, rates of filtration, and other parameters in order to achieve the desired therapeutic targets planned by the treating physician and set in the original prescription.
Healthcare is now definitely far from the original scenario where physicians and nurses had to struggle with rudimentary machines in order to deliver a safe and effective treatment. Those times are gone. Often the dialysis machine is seen as a black box where nothing can be modified from the scheduled functionality and the machine is automatically selecting the best operational mode to achieve therapeutic targets. Thus, it is not wrong to say that dialysis technologies have significantly advanced over the years and are continuing to advance; albeit have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as difficult to remove. Therefore, dialysis membrane innovation is currently directed toward enhanced removal of uremic toxins and increased membrane permeability. With a new generation of hemodialysis membranes, meaningful clearance of these molecules is now possible.
The burden of end-stage renal disease (ESRD) is rising dramatically in India, with the proportion of deaths due to kidney failure increasing yearly. The age-adjusted incidence of ESRD in India is 226 per million population. It is estimated that nearly 220,000 new ESRD patients are added to the pool every year. Dialysis is the only life-sustaining treatment modality for these patients. The shortage of nephrologists, late referral of patients, inadequate health awareness about preventive measures, and a lack of more cost-effective alternatives like renal transplantation or peritoneal dialysis are important issues in the provision of care to ESRD patients. Unequal distribution of nephrologists, with a concentration in large cities and in the private sector is a major barrier to equitable provision of dialysis to all sections of the society. There is a need to bridge the gap between patients and doctors through technological intervention. Inadequate insurance coverage further aggravates the situation.
Although access to dialysis, particularly hemodialysis, has increased in recent years, only a minority of patients are able to continue long-term hemodialysis, mostly because of the high costs. Making dialysis available to all who can benefit from the therapy will create an additional demand for 34 million dialysis sessions in India. Taking into account the financial pressures on the affected households, the government of India announced the Pradhan Mantri National Dialysis Program to provide free dialysis services to the poor in public sector hospitals. Implementation of this ambitious program involves major augmentation of existing service delivery infrastructure. Alternatively, the government may consider purchasing dialysis services from the private sector. Presently, the program is in its nascent stages in India. The proposed program aims to deliver dialysis services to the poor through a public–private partnership mode. In this program the private partner provides for medical human resources, dialysis machines, water treatment infrastructure, dialyzer, and consumables. Till now, the government has performed more than 22 lakh dialysis sessions for 2.25 lakh patients in more than 500 districts under the program.
Made-in-India dialysis machines undergo clinical trials
Bangalore-based researchers have recently launched a Made-in-India dialysis machine, which is expected to reduce cost of the medical procedure. Designed by Renalyx Health Systems, the machine, RxT17, started undergoing successful clinical trials at JSS Medical College Hospital, Mysuru, since March 2, 2018. Dialysis machines are being imported from Germany, Sweden, and China at an average unit cost of `10 lakhs, resulting in a dialysis session costing between `2500 and `4000. The newly developed machine is likely to be priced at `4 lakh and reduce the cost of a session to `1000. The machine is cloud-enabled and can be connected to a mobile app, so that nephrologists can monitor its functioning and the patient’s response remotely. This would facilitate access in rural areas too, given its ability to connect seamlessly and its capacity to run on solar power.
Global market dynamics
The global dialysis equipment market has been estimated to be valued at USD 14,783.7 million in 2018, and is expected to expand at a CAGR of 4.8 percent from 2018–2028, estimates Future Market Insights. Growth of the market is mainly driven by the high prevalence of CKD, worldwide. The use of dialysis over kidney replacement, aging epidemiology, product innovation, and wide product portfolio drive market growth. Focus on patient-caregiver connectivity, though the global dialysis equipment market is expected to witness impressive growth over the years. However, healthcare laws and regulations are factors expected to hamper market growth.
In terms of value, the hemodialysis devices segment has been estimated to account for 60.4 percent share of the global dialysis equipment market by 2018, and is projected to register a healthy CAGR of 4.6 percent in terms of value. The CRRT segment is expected to witness a growth rate of 6.8 percent attributing to the relatively less time for the suturing process as compared to the conventional approach.
North America is projected to dominate the global market in terms of revenue share. The foray of leading North American companies into the hemodialysis devices market over the last few years is a factor expected to boost overall sales of these devices in the region. APEJ and Japan are expected to witness significant growth owing to significant investments in healthcare infrastructure, and increasing geriatric population in these regions.
The key players in the market focus on various strategies such as expansions; product launches and product enhancements; mergers and acquisitions; and partnerships, agreements, and collaborations in order to strengthen their global position. Expansion was the key growth strategy adopted by a majority of the industry players to increase their share in the dialysis market. Companies as Fresenius Medical Care, Baxter International, DaVita Healthcare Partners, Diaverum Deutschland, B. Braun Melsungen, Nipro Corporation, NxStage Medical, Asahi Kasei Medical, Nikkiso, and Mar Cor Purification majorly adopted this strategy. Apart from geographic expansion, a number of leading players adopted the strategy of product launches and enhancements to develop new and technologically advanced dialysis products and treatment, strengthen their product portfolios, upgrade existing products, and address the unmet needs of end users.
In the last decade, the technological innovations implemented in dialysis equipment and its new therapeutic modalities have improved the quality and safety of renal replacement treatments allowing this group of more unstable patients to benefit from a better tolerance to the procedure and quality of life.
Ultrathin graphene membrane. A significant advancement has been made with a medical device, in the form of a dialysis membrane, with the super-material graphene at its core. This is a change from the core use of graphene, which is used with electronic components. Massachusetts Institute of Technology scientists have fabricated a functional dialysis membrane from a sheet of graphene. The new graphene membrane is no large than a fingernail and it is, remarkably, less than 1 nm thick and works 10 times faster than current membranes. The ultrathin material is exceptionally sturdy, remaining intact under applied pressures of at least 100 bars.
Medium cut-off membranes. The newest generation of highly selective and permeable medium cut-off (MCO) membranes meet requirements for both high quality and good performance for dialysis treatment, featuring the removal of large middle-molecules typical of a high cut-off membrane, and the low removal of albumin as in state-of-the-art high-flux membranes. For uremic solutes, MCO membranes offer improved clearance compared with that of high-flux membranes used in the hemodialysis mode and equivalent clearance to that of high-flux membranes in the high-volume mode. The benefit is performance equivalent to that of high-volume HDF without a need for the online production of substitution fluid or for vascular access required for high blood flow rates. These special MCO membranes should raise the standard of treatment available for all chronic hemodialysis patients, potentially decrease inflammatory responses, and generally improve patient outcomes.
Miniaturized wearable artificial kidney. The wearable artificial kidney (WAK) could be the most significant technology advance since the development of the long-term dialysis methods in the 1960s. Although in the past it was fixed to the body via a 10-pound belt, recent technological advancements have introduced smaller and lightweight WAK devices. The newly developed miniaturized WAK weighing 2 pounds appears to be at the tail-end of its third round of human trials and is getting closer to market release. To achieve the smaller size, researchers reduced the weight of the pump by using light yet hard plastic or graphite instead of stainless steel. In addition, the battery is smaller and can be recharged at night. The new motor does not require a gearbox, saving space and weight. The wearable device can now be attached to a patient’s body and comfortably be worn underneath clothes throughout the day.
Implantable artificial kidney. Researchers at the University of California, San Francisco (UCSF), are developing an implantable artificial kidney that can closely replicate the functions of a real kidney. The implantable bioartificial kidney is an alternative to devices that would tether patients or limit their mobility. The Kidney Project, as a national research initiative is named, centers on development and testing of a surgically implanted, freestanding bioartificial kidney that performs the vast majority of filtration, balancing, and other biological functions of the natural kidney. Powered by the body’s own blood pressure, the device does not require external tubes or tethers associated with WAK. The two-part implanted artificial kidney incorporates recent developments in silicon nanotechnology, which makes it possible to mass-produce reliable, robust, and compact filtering membranes.
Nano-filter artificial kidney. The nano-filter works as a tiny dialysis machine, almost like a small portable kidney. The unit connects to dialysis ports on the neck and the patient can go on with their day. With this constantly working nano dialysis machine, renal failure patients would not need clinical dialysis at all. This artificial kidney is being developed as wearable technology. The device fits in the palm of the hand and has a pore size of less than 10 nm, or smaller than 10 billionths of a meter. It is attached to catheters now used by dialysis patients and could be used to continually filter their blood, rather than three times a week.
AI – the future
Current dialysis devices are not able to react when unexpected changes occur during dialysis treatment or to learn about experience for therapy personalization. Furthermore, great efforts are dedicated to develop miniaturized artificial kidneys to achieve a continuous and personalized dialysis therapy, in order to improve the patient’s quality of life. These innovative dialysis devices will require a real-time monitoring of equipment alarms, dialysis parameters, and patient-related data to ensure patient safety and to allow instantaneous changes of the dialysis prescription for the assessment of their adequacy. The analysis and evaluation of the resulting large-scale data sets enters the realm of big data and will require real-time predictive models. These may come from the fields of machine learning and computational intelligence, both included in artificial intelligence (AI). The incorporation of AI should provide a fully new approach to data analysis, enabling future advances in personalized dialysis therapies.
However, AI research on dialysis is still in an early stage, and the main challenge relies on interpretability and/or comprehensibility of data models when applied to decision making. Artificial neural networks and medical decision support systems have been used to make predictions about anemia, total body water, or intradialysis hypotension and are promising approaches for the prescription and monitoring of hemodialysis therapy. Current dialysis machines are continuously improving due to innovative technological developments, but patient safety is still a key challenge. Real-time monitoring systems, coupled with automatic instantaneous biofeedback, will allow changing dialysis prescriptions continuously. The integration of vital sign monitoring with dialysis parameters will produce large data sets that will require the use of data analysis techniques, possibly from the area of machine learning, in order to make better decisions and increase the safety of patients.
Nearly 2.5 lakh people in India die due to kidney diseases every year and this has emerged as a major challenge for the medical fraternity. However, over the years some medical innovations are making big breakthroughs in kidney treatment. Artificial kidney and portable dialysis machines are among those innovations which are proving very effective. Moreover, in the near future, a CRRT machine capable (via complex algorithms and closed loops) of automatically deciding how to optimize dose prescription in order to reach a preselected dialytic target can be seen. This case considers an advanced level of automatization in CRRT that, although not possible today, will probably represent the routine in the next generation’s critical care ward. The dialysis market in India is estimated to be growing at the rate of 31 percent per annum. To fulfill current and future demands for dialyzers, large-scale manufacturing is required. The production of membranes and dialyzers requires advanced and automated manufacturing technology to fulfill the specific quality needs for medical applications and the continuously increasing demand.