Author: Kenneth J. Woodside, MD
The goal of renal replacement therapy is to replicate native kidney function. To date, only kidney transplantation approximates native kidney function, providing continuous filtration with physiological responses (e.g. renin-angiotensin-aldosterone axis) and hematopoietic hormonal function (i.e. erythropoietin). Traditional in-center hemodialysis has certainly had iterative improvements over the decades, but still does not provide continuous renal function. Home hemodialysis and peritoneal dialysis shorten the interval between dialytic sessions significantly, resulting in improved outcome. However, even these modalities do not match kidney transplant outcome nor native kidney function. Xenotransplantation and stem cell with scaffold-based kidney constructs or organoids have the potential to replicate native kidney functions, including those related to endocrine and hematopoietic functions, both of which have significant potential.
The Advancing American Kidney Health Executive Order that specifies a focus on at-home renal replacement therapies, along with the KidneyX Prize Innovation Accelerator sponsored by the U.S. Department of Health and Human Services and the American Society of Nephrology has resulted in some disruptive developments both for focus of dialysis modality, with increased utilization of peritoneal dialysis, changes in the transplant regulatory approach and organ allocation approaches, and even in renal replacement therapy devices themselves.
Ideally, renal replacement devices would be continuous, ambulatory, portable, with minimal access problems. The spectrum of developing technologies works progressively towards these goals: traditional dialysis improvements, home hemodialysis, portable hemodialysis, wearable dialyzers, and implanted renal replacement devices and constructs. While developments in xenotransplant and stem cell-based constructs and organoids are often topics for the transplant literature and meetings, discussion of devices for mobile, wearable, or implantable hemodialysis tends to be centered in the nephrology and dialysis access literature and meetings.
Home hemodialysis units are smaller than traditional, in-center, dialysis machines. However, they are still dependent on an adequate water supply and a large volume of dialysate, as they rely on the same single-pass proportioning for the dialysate that traditional dialysis systems use. Over the last few years, there has been improvements in the size and function of such machines. More recently, true portable machines are in development, including some that are relatively independent of a significant continuous water supply using sorbent technologies. Sorbent approaches pass the effluent (used) dialysate throw a cartridge containing a disposable absorbent which allows reuse of the dialysate, greatly decreasing the required volume.
True wearable hemodialysis devices have reached limited human trials. Such devices have low continuous clearance rates and function more like continuous venovenous hemodialysis (CVVHD). The dialysis unit is external to the body, often on a wearable vest or backpack. Vascular access has been somewhat problematic, as the successful trials have had to rely on central venous catheters for safety purposes, due to the risk of sudden accidental decannulation of a traditional arteriovenous fistula or graft.
Implantable renal replacement devices are on the horizon, with several different approaches being developed. As the connection of the device to the bladder is fraught with infection risk, some of these devices have a wearable or episodic external component, which is particularly anticipated in first generation devices. Like wearable approaches, these devices rely on low continuous clearance rates, with some having times of greater clearance. As these devices are implanted, they do not have the same risk of accidental decannulation that wearable devices, although the risk of foreign body infection is higher. Dialysis and filtration are achieved either by mechanico-osmotic means (e.g. like CVVHD) or using an implantable bioreactor and membrane. These devices must be designed to avoid taking much of the space that a kidney transplant would use, so need to be somewhat small. While some devices use the pressure differential between the arterial inflow and venous outflow to drive the blood across the dialysis, at least one uses the normal systolic-diastolic differential of the arterial system to flux blood past the membrane, thereby avoiding the need to sacrifice a portion of the venous outflow of a future kidney transplant—something particularly important in patients with a history of multiple dialysis accesses and catheters.
The definition of a true artificial kidney is somewhat elusive, although it should include a way to only sporadically require recharge or revision and a pathway to eliminate metabolic and volume waste regularly without issue—hopefully by connecting to the bladder. As urinary tract colonization and infections are common, it is anticipated that intermediate stage artificial kidneys may be better defined as implantable dialysis devices. Ideally, an artificial kidney would also provide hematopoietic function, but as this function of the kidney is easily pharmacologically mimicked, that is not actually necessary.
Artificial kidneys, stem-cell and scaffold grown kidneys, or xenotransplant are all on the horizon. Likely, each will have specific advantages and disadvantages for different subsets of patients. For example, someone with a significant cancer burden may be better served by a mechanic-osmotic device, while someone with risk of infecting a foreign body or need to avoid anticoagulation might be better serviced with a stem cell and scaffold kidney or xenograft. The increased number of options can only serve to better match the most appropriate renal replacement approach to each patient.