Develop components of the blood circuit that allow for hemodialysis without the need for systemic anticoagulation

Develop PD access with improved drainage characteristics, including prevention of outflow failure

Develop PD access with reduced risk of infection

Develop a safer vascular access capable of preventing (e.g., needle-free) or mitigating (e.g., self-sealing) catastrophic events of a vascular access disconnect

Develop a vascular access with fewer or no interventions needed to maintain patency

Develop methods for early detection/diagnosis of access-related infections

Develop novel biomaterial-based conduit or endothelial cell-lined robust conduit (i.e., stent) that permits delivery of blood to the filtration unit

Develop access that is non-intrusive and functionally acceptable, easy and quick for the patient to connect and disconnect, secure with minimal discomfort (e.g., skin-level or sub-cutaneous access), and aesthetically pleasing to patients

• Hemodialysis (Near-term)
• Wearables (Mid-term)
• PD Access (Near- and mid-term)

Develop entire blood circuit that allows for hemodialysis with minimal or no use of anticoagulants or anti-clotting agents

Develop vascular access with internal connection to the native vasculature that maintains patency without the need for systemic anticoagulation

Develop vascular access that significantly reduces the risk of infection over the life of the implant

Identify and/or develop potential materials with desired scaffold properties (mechanical, porosity, degradation) for structural support/scaffold development, as well as scaffold manufacturing techniques. In addition, these scaffolds must be biocompatible and porous to allow for movement of reabsorbed fluid and allow ready access for secretion of toxins into the processed filtrate

Develop a scaffold or membrane device capable of allowing oxygenation and nutrient access for transporting epithelial cells and demonstrate activity ex vivo

Develop and demonstrate structural support/scaffold that maintains desired function in vivo

For systems using sorbents, develop new sorbents with fewer adverse electrolyte changes, no generation of potentially toxic byproducts, greater uremic toxin capacity, and ability to be regenerated between uses

Identify gene modifications needed to address coagulation incompatibilities, antibody-mediated rejection, inflammatory responses, etc., for xenotransplantation

Genetically engineer animal to inactivate viral and pathogenic organisms for xenotransplantation

Identify appropriate genetic modification and immunological characterization pre-screening methods/ regimens, as well as pharmacological interventions, for xenotransplantation from animals to humans

Standardize panel of immune markers to assess tolerance of RRT product (i.e., minimize immune rejection

Generate suitable transgenic donor animals for xenotransplantation

Demonstrate induction of immune tolerance

Demonstrate long-term graft survival in nephrectomized animals

Recruit host vessels to implanted cellular product and demonstrate perfusion of implanted tissue that is sufficient to maintain cell health and physiological functions

Establish coordinated registry network of real-world safety and efficacy data

Develop technologies to allow real-time treatment monitoring by various sensors (flow, pressure, volume status, electrolytes, etc.) that can be observed/tracked by patients and providers

Develop online sensors (e.g., for ammonia or other uremic toxins or byproducts) to alert users that sorbent cartridges need to be replaced

Identify in vitro surrogate assays or biomarkers for assessing safety and proper functioning of the KRT

Develop sensors that can provide feedback on body fluid volume and blood concentrations of key components (e.g., potassium, sodium, calcium, phosphorus, pH)

Develop technologies that detect a vascular access disconnect and/or act to avoid blood loss in the event of a disconnect (e.g., a sensor that integrates with software to stop the blood pump and put replacement product in safe mode)

Establish criteria for safety testing necessary before and after human trials to guide developers and allow for projections of development timelines

Develop a mechanism to monitor the integrity of the biological product itself (e.g., clotting, when to replace cells)

Develop integrated systems that use sensor input to allow adjustment in real time or as part of a closed-loop system

Develop technologies to detect and proactively mitigate clotting

Develop mechanism to prevent or deal with gases accumulated by the product

Conduct in vivo testing to evaluate safety (e.g., toxicity), integrity, longevity, and tolerance of RRT product

Develop lightweight rechargeable batteries capable of powering KRT systems

Develop systems that allow for safe, secure, and efficient two-way communication between the product/implant and the operator

Develop miniaturized systems (e.g., sorbents) capable of regenerating spent dialysate

Develop blood/filtrate/dialysate pumps that are miniaturized, low-energy, and hemocompatible

Develop lightweight power source capable of powering KRT systems that can be recharged using wireless energy transfer

Develop miniaturized, efficient systems to generate sterile water for replacement fluid/dialysate generation

Inform how current standards and regulatory recommendations (e.g., existing guidance documents) can be applied to novel KRT technology, and develop stakeholder working groups to address and publish findings on any identified gaps in testing recommendations (after review of existing standards and guidance)

Review existing literature and publish findings on best practices for animal models and animal studies used for testing KRT systems

Clarify the different regulatory pathways for device-only systems, cellular/device combination systems, and cell- based/xenotransplantation products

Increase understanding and awareness of 1) communication mechanisms (e.g., Pre-Submission, INTERACT) that enable developers to obtain early, non-binding, regulatory advice from the US Food & Drug Administration, and 2) expedited programs intended to facilitate development and review of eligible KRT products

Develop sources of real-world data (e.g., patient registries) that could be used both to help objectively measure iterative improvements in evolving technologies, as well as garner information to support regulatory decision-making

Inform the most appropriate clinical trial designs (including randomized trials and data generation and management) to support product development, safety, approval, coverage, and reimbursement

Qualify and make publicly available Medical Device Development Tools (MDDTs) that can be used by the community to streamline device development and regulatory evaluation³³

Develop uniform technology licensing agreement to broaden participation and facilitate collaboration, while allowing contributors to maintain intellectual property rights

Develop and provide a pre-competitive forum for annual scientific exchange, networking, sharing, and collaboration

Assess scientific advancement and facilitate regular updates to the technology roadmap

Identify gaps and develop necessary educational and scientific tools that may assist innovators with non-nephrology backgrounds to accelerate translation of current technology

Develop and maintain a catalog of research and technology advancements to accelerate efficient and coordinated technology development

Facilitate dialogue with parties that have KRT innovation financing models in place and co-investments from foundations, patient associations, payers, and governments to identify and implement best practices

Conduct thorough assessment of existing and in-development KRT systems and associated technology readiness levels (TRLs) to set a baseline for innovation

Identify potential changes to the current Medicare ESRD Prospective Payment System model that could encourage KRT investment and innovation