Novel Extracorporeal Technology for Kidney Disease

PROJECT SUMMARY/ABSTRACT Hyperphosphatemia occurs in up to 90% of patients on hemodialysis (HD), with concentrations above the clinically acceptable threshold of 3.5 to 5.5 mg/dL in ~50% of patients despite being prescribed low-phosphate diets and oral phosphate-binding medications. Despite being widely prescribed, oral phosphate-binding drugs possess finite binding capacity (40-50%), poor compliance secondary to multiple doses and tablets per day, potential absorption of aluminum, undesirable side effects, and considerable costs. Also, the level of phosphate reduction with these agents in clinical research studies are not typically observed in real world data. Mortality rates in chronic kidney disease patients increase as a function of blood phosphate levels and this contributes to the 10- to 20- fold higher rate of death in HD patients vs. age-matched controls. The KDIGO guidelines recommend increasing dialytic phosphate removal and lowering blood phosphate levels toward the normal range. Prevention of a positive phosphate balance requires an increase in removal of 200-450 mg per HD session (3x/week) – a capacity that is not feasible for conventional diffusion-based 4 h HD sessions. We hypothesize that the addition of a stand-alone phosphate adsorption device to the existing diffusion- based conventional HD procedure has the potential to enhance phosphate removal from blood and reduce net positive body burden. The overall goal of Katharos’ Phosfilter device is to reduce the incidence of high phosphate-associated morbidity and mortality, diminish reliance upon out-of-clinic patient compliance and out-of-pocket costs associated with oral drugs and create a simplified treatment approach for patients that enhances attainment of clinical KDIGO benchmarks for phosphate concentrations (2.8-4.5 mg/dL). The proposed mechanism for the removal of phosphate from body tissues by the Phosfilter is through the development of a peripheral phosphate sink to the blood. The proposal’s Specific Aims will test device prototypes on the benchtop and ex vivo and evaluate the efficacy, safety, hemocompatibility, biocompatibility and phosphate removal kinetics of the device in a canine model of naturally occurring kidney disease. The results of the proposed canine studies will serve as a critical benchmark to proceed with the development of the device for human use. This clinical and translational feasibility study integrates Katharos, Inc., nephrology experts in metabolic bone disease, and clinicians caring for humans and animals with kidney disease. Katharos, Inc. seeks to advance novel science toward commercialization of medical innovations for ESRD patients.