Despite overwhelming evidence that the complement system is involved in kidney and cardiovascular outcomes, stringent technical requirements limit its inclusion in clinical trials and diagnostics. Current protocols require careful sample collectin, immediate freezing, and shipping to only a few specialized labs. As a result, while complement system proteins C3 and C4 are routinely measured in autoimmune disease clinics, proteolytically activated split products known to mediate active inflammatory and autoimmune processes are rarely assessed. Kypha Inc. is developing an integrated point-of-care (POC) platform to make reliable complement data more accessible to clinical trials and diagnostic applications. These efforts are timely due to recent therapeutic development focused on anti-inflammatory strategies including complement inhibition for extracorporeal therapies (such as hemodialysis), autoimmunity, transplant rejection, and other conditions. Milestones in this Phase I proposal will demonstrate the feasibility of using advanced multiplex quantitative lateral flow assays in the point of care as a solution that decreases the resources required to measure complement activation and inflammation in clinical trials, paving the way for their full utility inthe diagnosis and management of acute and chronic renal and vascular inflammatory diseases.
Public Health Relevance Statement: Public Health Relevance: Complement activation is a known mediator of inflammatory renal and vascular pathophysiology. However, protein instability in vitro requires stringent sample handling and laboratory requirements that limit the inclusion of complement biomarkers in clinical trials. Rapid, simple, and comprehensive complement assays will make reliable complement data more accessible. This project will establish point of care biochemical data collection as a feasible approach for improving anti-inflammatory clinical trials in hemodialysis and other renal conditions.
NIH Spending Category: Autoimmune Disease; Clinical Research; Clinical Trials and Supportive Activities; Kidney Disease
Project Terms: Academic Medical Centers; Acute; Address; Anti-inflammatory; Anti-Inflammatory Agents; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Biochemical; Biological Assay; Biological Markers; biomaterial compatibility; Blood; Cardiovascular system; Caring; cell injury; Chronic; Chronic Kidney Failure; Clinic; Clinical Trials; Collectins; commercial application; Complement; Complement Activation; complement C4d; complement system; Data; Data Collection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostics Research; Disease; Disease Management; Enzyme-Linked Immunosorbent Assay; Freezing; Functional disorder; glucose monitor; Goals; graft function; Graft Rejection; Hemodialysis; improved; improved outcome; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; inflammatory marker; Interleukin-6; Intervention; Kidney; kidney vascular structure; Kinetics; Laboratories; Lateral; Maintenance; Marketing; Measures; Mediating; Membrane; Monitor; Multi-Institutional Clinical Trial; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; point of care; Process; Proteins; Protocols documentation; public health relevance; Research; Research Personnel; Resources; Sampling; Savings; Shipping; Ships; soluble complement C5b-9; technological innovation; Technology; Testing; Therapeutic; therapeutic development; Time; TNF gene; Transplantation; Vasculitis
