Solutions
A New Kidney Replacement Therapy Paradigm
The roadmap outlines multiple solution pathways for achieving a new kidney replacement therapy (KRT) paradigm that offer greater opportunity for near-term incremental improvements as well as longer-term solutions and more disruptive breakthroughs.
Solution Categories
Regardless of the category or type of product developed to replace the damaged or failed kidney functions, all KRT solutions should:
- Improve patient quality of life
- Extend life for those living with kidney failure
- Be able to be manufactured at a scale that makes the products widely available
Definition
Innovations to existing dialysis therapies (hemodialysis [HD], peritoneal dialysis [PD], vascular access) that improve quality of life, reducing disease complications and increasing treatment flexibility.
Patient-Centered Solution Characteristics:
- Non-invasive
- Potential home use
- Better ease of use for more self-care
- Fewer complications compared with current dialysis therapy
- Improved clearance to uremic toxins
Definition
KRT products that are transportable to expand treatment location options beyond the home and clinic (e.g., work, travel)
Patient-Centered Solution Characteristics:
- Non-invasive
- No bigger than a carry-on suitcase
- Enables shorter duration, more frequent or continuous treatments, alleviating dietary restrictions and pill burden
- Enables temporary leave from in-center dialysis
Definition
KRT products that are worn on the body during use, allowing for continuous or near-continuous treatment and enabling increased ability to work and engage in other lifestyle activities
Patient-Centered Solution Characteristics:
- Non-invasive
- Not larger than a backpack
- Increases freedom of movement to permit normal daily activities
- Replaces need for in-center dialysis
Definition
A surgically implanted KRT product— device, combination biologic/ device, or biological product, including xenotransplant (living cells or tissues from another species)—that closely mimics normal kidney physiology or restores endogenous kidney function
Patient-Centered Solution Characteristics:
- More invasive
- Reduced maintenance and interventions
- Ability to completely resume normal daily activities
- Low reversibility due to surgical intervention
- Need for immunosuppression and anticoagulation varies
Minimum Design Attributes
Any technology solution must strive to meet these minimum technical attributes, regardless of approach. Optimal solutions should aim to meet all design requirements, with intermediate solutions offering more short-term and partial solutions to those receiving KRT.
Definition
The vascular, peritoneal, blood circuit, or alternative (e.g., GI tract) access needed for treatment
Patient Impact
Safer, more continuous treatment with fewer complications and reduced need for interventions
Minimum Technical Design Attributes:
- Provides access to the blood (either direct or indirect via peritoneal membrane or GI tract) for filtration in a continuous manner
- Maintains patency over usable life, reducing incidence of stenosis and thrombosis
- Lowers incidence of infectious complications
- Patient-friendly (low/no maintenance, easy and quick connection/disconnection, painless access)
- Composed of biocompatible materials
- Mitigates blood loss or other complications in the event of an unintentional disconnection
Definition
Filtering of blood to remove waste and excess fluid
Patient Impact
Access to a safe, effective, longer-life, easy-to-use filtration system that avoids clotting issues
Minimum Technical Design Attributes:
- Non-fouling and able to maintain continuous performance (duration defined by product and clinical context)
- Generates a filtrate of at least 40L/day (~30mL/minute for 24-hour therapy)
- Size selective, with no loss of essential blood proteins (e.g., albumin)
- Component materials and design must be biocompatible and hemocompatible
Definition
Maintaining appropriate levels of key components in the blood
Patient Impact
More comprehensive and effective regulation of electrolytes, resulting in reduced need for dietary restrictions or supplements
Minimum Technical Design Attributes:
- Normalizes and maintains commonly measured or needed electrolytes (e.g., sodium, potassium, calcium, magnesium, and phosphate) within clinically acceptable ranges, potentially with the aid of pharmacological interventions
Definition
Regulating the amount of body fluid and/or removing excess fluid
Patient Impact
Ability to personalize and optimize the amount and rate of excess fluid removal, resulting in stable blood pressure with less dehydration and cramping
Minimum Technical Design Attributes:
- Has the capacity to remove excess fluid and is adjustable based on the needs of the patient
- Allows patient to self-manage and monitor fluid status separate from monitoring of other functions (electrolyte and toxin removal)
Definition
Limiting or preventing toxin accumulation in the bloodstream and throughout the entire body
Patient Impact
Reduced presence of harmful toxins in the bloodstream that could lead to uremic toxicity and/or drug toxicity
Minimum Technical Design Attributes:
- Maintains clearance/reduction of the three categories of uremic toxins:
- small, non-protein bound (clearance of 40L/day)
- small, protein-bound (reduction in blood concentration)
- "middle molecules" (reduction in blood concentration)
- Capable of secreting non-filtered toxins
Definition
Removing excess filtrate after processing; connectivity for filtration, processing, and exterior drainage
Patient Impact
Drainage processes and equipment that are safe and effective, with acceptable characteristics (e.g., size, weight, comfort, appearance, compatibility with sanitary infrastructure)
Minimum Technical Design Attributes:
- Composed of biocompatible materials
- Removes remaining processed filtrate—up to 3L/day
- Processed filtrate storage/removal apparatus is acceptable to the patient
Regulatory Framework for Innovative Products
Innovative KRT solutions will likely take many forms—even some not yet conceptualized or defined. Each product type may have different regulatory considerations or pathways for product development, commercialization, and patient access. Refer to A Guide to Regulatory Resources for the Product Developer for more information.
Device
An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article that affects kidney structure or function, and does not achieve its primary intended purposes through chemical action within or on the body (defined in 21 CFR 321(h))
Regulated by the FDA Center for Devices and Radiological Health (CDRH)
Combination Product
A product composed of two or more regulated components (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic), that are physically, chemically, or otherwise combined or mixed and produced as a single entity; packaged as a unit; or intended for use together (defined in 21 CFR 3.2(e))
Assigned to an FDA center (CBER, CDRH, or the Center for Drug Evaluation and Research [CDER]) based on a determination of the product's primary mode of action31
Biologics
A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product applicable to the prevention, treatment, or cure of a disease or condition of human beings. Examples of analogous products include cell and gene therapies, human tissue-derived materials, and live biotherapeutic products (defined in 42 U.S.C. 262(i))
Regulated by the FDA Center for Biologics Evaluation and Research (CBER); biologics regulated by CDER include monoclonal antibodies for in vivo use and other products32