A Technology Roadmap for Innovative Approaches to Kidney Replacement Therapies: A Catalyst for Change

Abstract

The number of patients dialyzed for ESKD exceeds 500,000 in the United States and more than 2.6 million people worldwide, with the expectation that the worldwide number will double by 2030. The human cost of health and societal financial cost of ESKD is substantial. Dialytic therapy is associated with an unacceptably high morbidity and mortality rate and poor quality of life. Although innovation in many areas of science has been transformative, there has been little innovation in dialysis or alternatives for kidney replacement therapy (KRT) since its introduction approximately 70 years ago. Advances in kidney biology, stem cells and kidney cell differentiation protocols, biomaterials, sensors, nano/microtechnology, sorbents and engineering, and interdisciplinary approaches and collaborations can lead to disruptive innovation. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, has convened a multidisciplinary group to create a technology roadmap for innovative approaches to KRT to address patients' needs. The Roadmap is a living document. It identifies the design criteria that must be considered to replace the myriad functions of the kidney, as well as scientific, technical, regulatory, and payor milestones required to commercialize and provide patient access to KRT alternatives. Various embodiments of potential solutions are discussed, but the Roadmap is agnostic to any particular solution set. System enablers are identified, including vascular access, biomaterial development, biologic and immunologic modulation, function, and safety monitoring. Important Roadmap supporting activities include regulatory alignment and innovative financial incentives and payment pathways. The Roadmap provides estimated timelines for replacement of specific kidney functions so that approaches can be conceptualized in ways that are actionable and attract talented innovators from multiple disciplines. The Roadmap has been used to guide the selection of KidneyX prizes for innovation in KRT.

Keywords: RRT access; United States Food and Drug Administration; biocompatible materials; blood filtration; chronic kidney failure; dialysis; electrolyte homeostasis; kidney; kidney bioengineering; kidney chimeras; kidney dialysis; kidney organoid; microtechnology; motivation; nephrology; proximal tubule; public-private sector partnerships; quality of life; renal dialysis; renal replacement therapy; secretion; toxicity; urinary tract physiological phenomena; stem cells; xenotransplantation.

Figure 1.

Comparison of survival of patients with ESKD compared with survival of patients with many forms of cancer. Patients with ESKD were divided into four categories: those with a living related transplant, deceased donor transplant or those on hemodialysis or peritoneal dialysis. *Reference population: patients with incident ESKD, 2011. Adjusted for age, sex, race, Hispanic ethnicity, and primary diagnosis. ESKD-DDTxp, ESKD received deceased donor transplant; ESKD-PD, ESKD receiving peritoneal dialysis; ESKD-HD, ESKD receiving hemodialysis; ESKD-LDTxp, ESKD received living donor transplant (40,41).

Figure 2.

An overview of the approach and considerations incorporated into the Roadmap. Milestones were identified in order of complexity: enhanced dialysis (improvements on current approaches), a portable or wearable solution, biohybrid/implantable kidney (including xenotransplantation), and a regenerated kidney. Kidney functions that would have to be replaced were grouped into five categories, including: blood filtration, fluid regulation, electrolyte homeostasis, toxin removal/secretion, and filtrate transport and drainage. How replacement would occur was not prescribed, but rather left to the ingenuity of the community. A number of “system enablers” could facilitate progress. These include, but are not limited to, kidney replacement access advances, developments in biomaterials, new insights into biologic and immunologic modulation, current advances in function, and safety monitoring. It was recognized that alignment with regulatory agencies throughout this development process was critical. It was also recognized that financial incentives and novel payment pathways would be very important to incentivize the innovation needed to accomplish the goals of the Roadmap. Figure is taken, with minor modifications, from the Roadmap (Supplemental Appendix 1). PD, peritoneal dialysis.

Figure 3.

Design criteria for innovative kidney replacement product or approach. Minimum technical design criteria were identified in six areas: KRT access, blood filtration, electrolyte homeostasis, fluid regulation, toxin removal/secretion, and filtrate transport and drainage. Figure is taken, with minor modifications, from the Roadmap (Supplemental Appendix 1). GI, gastrointestinal; KRT, kidney replacement therapy.