Need for a patient-centered innovation in dialysis

There is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible, and offer improved patient outcomes.

Early pioneers, such as Willem Kolff and Belding Scribner pioneered dialysis, which ushered in various significant improvements in the epidemiology, economics, and ethical frameworks for the treatment of renal failure. Despite a fast rise in the provision of dialysis – particularly hemodialysis – the rate of actual patient-centered innovation has slowed, particularly in high-income countries (HICs). Present trends are especially troubling from a global perspective – current expenses, even for HICs, are unsustainable, and most individuals who suffer renal failure do not seek treatment, resulting in millions of fatalities each year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible, and offer improved patient outcomes.

Patients are increasingly interacting with nephrology experts to define their preferences for meaningful outcomes that may be used to track progress. The underlying message of this interaction is that while patients value longevity, symptom relief and maximum functional and social rehabilitation are more important. Patients, payors, regulators, and healthcare systems are all seeking better value, which can only be achieved via real patient-centered innovation that promotes high-quality, high-value care. Significant efforts are currently being made to facilitate the necessary transformational transformations. International coordination and harmonization are required to catalyze, promote, and encourage these initiatives.

The status quo of dialysis care is suboptimal. Residual symptom burden, morbidity and mortality, and economic cost are all unacceptable, which begs the question of what steps are needed to change the established patterns of care. Patients are currently unable to live full and productive lives owing to the emotional and physical toll of dialysis, its intermittent treatment schedule, the dietary and fluid limitations, and their highly restricted mobility during treatment. Current technology requires most patients to travel to a dialysis center, and current modalities are non-physiological, resulting in washout, which is defined as extensive fatigue, nausea, and other adverse effects, caused by the build-up of uremic toxins between treatments and the rapid removal of these solutes and fluids over 4-h sessions in the context of hemodialysis. Low-income and middle-income countries face additional difficulties in the provision of dialysis owing to infrastructural requirements, the high cost of this treatment, the need for a constant power supply, and the requirement for high volumes of purified water.

Still, there has been a lack of drive to improve the procedure, in part because the treatment has proved highly profitable for dialysis providers around the world.

One of the big problems with modern dialysis is that the machines require vast amounts of water – 120 to 180 liters for each 4-hour session. Obviously nobody can carry that around them because it would weigh tons. There are a few in-home models marketed as portable – Fresenius sells a device that it says gives patients more mobility. It weighs 34 kilograms and can be used with a home tap, as long as the water meets certain quality standards. But the first priority in making dialysis more convenient is to remove the need for an external water supply.

In Seattle, CDI researchers have developed a technique that pushes the used dialysis solution through a cartridge that uses light to convert urea – a key toxin targeted by dialysis – into nitrogen and carbon dioxide, so that the solution can be recycled. The method can remove 15 grams of urea in 24 hours, sufficient for most people with kidney failure, and requires only 750 milliliters of solution. The team’s standalone hemodialysis device could be made compact enough to fit inside a rolling case, weighing no more than 9 kilograms. Ideally, patients would use it daily.

Another group trying to downsize dialysis was recently formed by the Dutch Kidney Foundation, the medical-devices firm Debiotech in Lausanne, Switzerland, and non-profit insurers. Its latest prototype, which it hopes to make available to patients by 2023, weighs about 10 kilograms and will require only 6 liters of solution. The device, which could be used at home, limits the quantity of dialysis solution needed by using an absorbent material to soak up the toxins.

In Singapore, researchers at the medical-technology company AWAK have been testing an even lighter device, one that weighs no more than 3 kilograms. It is designed for peritoneal dialysis, a technique that uses a catheter to send dialysis solution into the abdominal cavity, where a lining (the peritoneum) filters out toxins from the blood so they can drain, along with the solution, into an empty bag.

The AWAK device relies on a pump and a cartridge to absorb toxins from the used solution so that it can be recirculated. Each daily treatment would last seven to ten hours. The company completed a safety trial involving 15 adults at Singapore General Hospital in 2018. It reported no serious adverse events, although some patients experienced abdominal discomfort or bloating. The device is one of several more-portable products in development that the FDA has agreed to expedite through its breakthrough devices program.

In some regions of the world, peritoneal dialysis is not an option, owing to the costs of shipping the heavy bags of solution. An international competition led by the George Institute for Global Health in Camperdown, Australia, in 2015 sought ways to improve access. The winning technology, developed by Irish engineer Vincent Garvey, incorporates a lightweight kit that includes sterile bags containing a dry mix (dextrose and salts), along with a water distiller the size of a bread box, which sterilizes the water used to make the mix. A month’s worth of supplies could be shipped in a box weighing 3 kilograms – a big improvement over a typical day’s supply, which weighs 8 kilograms. The clinical trial is expected to complete by the end of next year.

Researchers at the University of California, San Francisco (UCSF), and Vanderbilt University in Nashville, Tennessee, have bypassed external devices and instead focused on developing a kidney prototype that they hope will one day be surgically implanted into a patient’s body. It would not require a pump because it would be attached to key arteries and powered by blood pressure. The device contains two key parts – a blood-filtration system and a cell-infused recalibration module.

The filter is made of silicon membranes with nanometer-scale pores that are designed to mimic the glomerulus. The recalibration module uses tubule cells from discarded human kidneys to rebalance the blood’s components. Late last year, researchers reported at an American Society of Nephrology meeting that they had conducted the first safety test of the recalibration module in pigs, without any of the serious problems often seen with implanted devices, including an immune reaction or blood clots.

This past year, three sheep in Canada have been wearing their kidneys on their sleeves. Or more aptly, in jackets on their fluffy backs. These three sheep are part of an ongoing animal study run by the Buffalo, New York-based startup Qidni Labs, a company pursuing waterless and mobile blood purification systems. Qidni Labs, founded in 2014, has raised USD 1.5 million and is currently in the due-diligence process leading up to another round of funding.

The jackets are a prototype of Qidni’s mobile hemodialysis machine called Qidni/D. The idea behind Qidni/D is that it will be significantly smaller than a traditional hemodialysis setup and use fewer fluids, allowing patients to be more mobile. In an early animal trial – the results of which have not yet been published in a peer-reviewed journal – the device was able to reduce levels of urea in sheep’s blood at the threshold of an adequate dose of traditional dialysis. These sheep had no functioning kidneys, and were hooked up to the machine for between four and eight and a half hours.

The data so far suggests that four hours of treatment should be sufficient to cleanse the sheep’s blood. This is just one small animal study, so it is hard to draw massive conclusions from it. It did not include an active control arm, for instance, and instead compared the amount of urea and electrolytes removed from the sheep’s blood to published standards from other studies on dialysis.

The team will continue to tweak the technology in more sheep-based studies and is aiming to begin human trials in 2022. The overall goal is to file for FDA approval, provided that clinical studies can demonstrate safety and efficacy, by the second half of 2023.

The past 50 years have seen rapid changes in how and to whom dialysis is provided. From a global perspective, the escalating numbers of patients who require dialysis mean that even current costs are not sustainable, and yet most people who develop kidney failure forego treatment owing to a lack of access, with millions of lives lost every year as a consequence. Also important, the limitations of current dialysis treatment in alleviating patient suffering, morbidity and mortality are now viewed as unacceptable. Consequently, patients, payors, regulators and healthcare systems are increasingly demanding improved value, which can only come about through true patient-centered innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalyzed, promoted, and fostered through international collaboration and harmonization to ensure that in the future, people living with kidney failure have more and better treatment options than exist today.