A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal Replacement Therapy in Critically Ill Children

危重儿童连续肾脏替代治疗期间反复抗凝和肾脏监测的低血容量平台

• 批准号: 10383224
• 负责人: VAMSEE K. PAMULA
• 金额: $ 26.61万
• 依托单位: BAEBIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-23 至 2023-05-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383224
• 关键词: Acid-Base Equilibrium; Activated Partial Thromboplastin Time measurement; Acute; Acute Renal Failure with Renal Papillary Necrosis; Adult; Alabama; American; Anemia; Anticoagulant therapy; Anticoagulation; Award; Biochemical; Biological Assay; Blood; Blood Tests; Blood Transfusion; Blood Urea Nitrogen; Blood Volume; Cardiac Surgery procedures; Chemistry; Child; Childhood; Clinical; Clinical Chemistry; Complex; Consumption; Critical Illness; Critically ill children; Custom; Development; Device or Instrument Development; Diagnostic; Dialysis procedure; Dose; Drops; Electrolyte Balance; Electrolytes; Equilibrium; Erythrocyte Transfusion; Excision; Extremely Low Birth Weight Infant; Factor Xa; Fluid Balance; Fluid overload; Funding; Goals; Guidelines; Hematology; Hemodialysis; Hemorrhage; Heparin; Heparinoids; Hospitalization; Human Resources; Iatrogenesis; Individual; Infant; Injury to Kidney; Intensive Care Units; Journals; Kidney; Kidney Failure; Laboratories; Lead; Left; Legal patent; Length; Liquid substance; Longevity; Manuscripts; Measures; Metabolic; Methods; Microfluidics; Modality; Monitor; Neonatal Intensive Care Units; Nephrology; Newborn Infant; Outcome; Patient Monitoring; Patients; Pediatric Hospitals; Performance; Phase; Phosphorus; Plasma; Potassium; Premature Infant; Procedures; Publications; Publishing; Reaction; Recurrence; Renal Replacement Therapy; Renal function; Reporting; Sampling; Small Business Innovation Research Grant; System; Technology; Testing; Time; Toxin; Transfusion; Ultrafiltration; Universities; Urea; Uremia; Validation; Whole Blood; acute care; assay development; base; comorbidity; critically ill newborn; design; digital; innovation; insight; instrument; microfluidic technology; mortality; neonate; novel strategies; pediatric patients; portability; professor; research clinical testing; risk minimization; usability

ABSTRACT A Low Blood Volume Platform for Recurrent Anticoagulation and Kidney Monitoring during Continuous Renal Replacement Therapy in Critically Ill Children (Fast-Track SBIR PA-20-260) Acute kidney injury (AKI) is characterized by a sudden decrease in the ability of the kidneys to adequately maintain electrolyte, acid-base, and fluid balance. Up to 30% of children admitted to intensive care units develop AKI and the presence of AKI is independently associated with increased length of hospitalization and higher rates of mortality. Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill children and is becoming increasingly common for newborns and small children (under 10 kg) with AKI and congenital kidney failure. Frequent monitoring (2-6 times a day) of anticoagulant therapy (heparin, heparinoids, etc.), kidney function (urea), and electrolyte composition (potassium, phosphorus, etc.) is necessary during the course of CRRT. Existing laboratory tests require large blood volumes, and the cumulative blood loss from routine bloodwork contributes to iatrogenic anemia. The majority of critically ill newborns (90% of extremely low birth weight infants and 58% of premature infants) will require red blood cell transfusions during their time in the neonatal intensive care unit (NICU) as a result of frequent blood draws. To meet the critical unmet need for rapid, low volume blood tests for CRRT monitoring in newborns and children, we will develop a panel of four assays on our near-patient digital microfluidic (DMF) platform to provide comprehensive profiling of anticoagulation dosing, kidney function, and phosphorus balance. Our innovative system will simultaneously measure anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), blood urea nitrogen (BUN), and phosphorus from < 50 µL of whole blood input. Plasma separation from whole blood (necessary for all four assays) will be automated on the cartridge to facilitate testing near the patient. By combining four technically complex assays (typically sent to different sections in a lab such as hematology and chemistry) into a single automated test, we can reduce sample-to-answer time and personnel time needed to perform each individual assay, and can significantly reduce the cumulative volume of blood required for recurrent monitoring over the full course of CRRT therapy. Our collaborators on this Fast-Track project include pioneers in pediatric acute care nephrology with multiple recent publications describing novel approaches to CRRT in newborns. Phase I of the project will establish feasibility of the proposed testing platform through development of DMF anti-FXa, aPTT, BUN, and phosphorus assays and demonstration of sufficient analytical and clinical performance. Phase II will combine the four assays into a multiplexed reaction with a time-to-result of under 15 minutes, evaluate the analytical performance and clinical concordance of each assay, and conduct onsite lead user testing of the system to establish reliability and usability. Our final product will initially be marketed for use in newborn and pediatric patients undergoing CRRT. Secondary markets will include both pediatric and adult patients undergoing cardiac surgery or other procedures associated with kidney failure, toxin removal, and ultrafiltration of fluid.

抽象的 连续肾脏期间复发性抗凝和肾脏监测的低血量平台 重症儿童的替代疗法 （Fast-Track Sbir PA-20-260） 急性肾脏损伤（AKI）的特征是肾脏足够的能力突然降低 保持电解质，酸碱和流体平衡。多达30％的儿童进入重症监护病房 AKI和AKI的存在与住院时间增加和更高 死亡率。连续肾脏替代疗法（CRRT）已成为首选的透析方式 对于重病的孩子，对于新生儿和小孩（10公斤以下）而变得越来越普遍 AKI和先天性肾脏衰竭。频繁监测抗凝治疗（肝素，每天2-6次） 需要肝素等），肾功能（尿素）和电解质组成（钾，磷等） 在CRRT过程中。现有的实验室检查需要大量的血液量，累积失血 从常规的血液起作用有助于医源性贫血。大多数重病新生儿（极度疾病的90％ 低出生体重的婴儿和58％的早产儿）在其时间内需要红细胞输血 由于血液频繁抽血而导致新生儿重症监护病房（NICU）。 为了满足对新生儿和儿童中CRRT监测快速，低量血液测试的关键需求， 我们将在我们的近乎病人的数字微流体（DMF）平台上开发一个四个测定的面板，以提供 抗凝剂量，肾功能和磷平衡的全面分析。我们的创新性 系统将简单地测量抗因子XA（抗FXA），激活的部分凝血蛋白时间（APTT），血液 尿素氮（BUN）和磷的全血输入。血浆与全血的分离 （所有四个测定法）将在墨盒上自动化，以促进患者附近的测试。经过 结合四个技术复杂的测定法（通常发送到实验室中的不同部分，例如血液学和 化学）进行单个自动测试，我们可以减少样本到答案的时间和人事时间 执行每个单独的测定 监测CRRT治疗的完整过程。 我们在这个快速轨道项目上的合作者包括儿科急性护理肾脏科的先驱 最近的出版物描述了新生儿中CRRT的新方法。该项目的第一阶段将建立 通过开发DMF抗FXA，APTT，BUN和Phosphorus，提出的测试平台的可行性 分析和临床表现的测定和演示。第二阶段将结合四个测定法 以低于15分钟的时间分配的多路复用反应，评估分析性能和 每项评估的临床一致性，并对系统进行现场负责用户测试，以建立可靠性和 可用性。我们的最终产品最初将被销售，用于新生儿和儿科患者接受CRRT。 二级市场将包括接受心脏手术或其他程序的儿科和成年患者 与肾功能衰竭，去除毒素和液体的超滤有关。