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 用于连续肾病期间反复抗凝和肾脏监测的低血容量平台 危重儿童的替代治疗 （快速通道 SBIR PA-20-260） 急性肾损伤（AKI）的特点是肾脏充分发挥功能的能力突然下降。 维持电解质、酸碱和体液平衡 入住重症监护病房的儿童中，高达 30% 会出现这种情况。 AKI 和 AKI 的存在与住院时间的延长和更高的住院时间独立相关。 连续肾脏替代治疗（CRRT）已成为首选透析方式。 对于危重儿童来说，对于新生儿和幼儿（10公斤以下）来说越来越常见 AKI 和先天性肾衰竭 经常监测（每天 2-6 次）抗凝治疗（肝素、 类肝素等）、肾功能（尿素）、电解质成分（钾、磷等）是必要的 CRRT 过程中现有的实验室检查需要大量的血液，并且需要累积失血量。 常规血液检查导致医源性贫血，大多数危重新生儿（90% 为重症新生儿）。 低出生体重儿和 58% 的早产儿）在出生期间需要输注红细胞 由于频繁抽血而被送往新生儿重症监护病房 (NICU)。 为了满足新生儿和儿童 CRRT 监测中快速、低容量血液检测的迫切需求， 我们将在我们的患者附近数字微流体 (DMF) 平台上开发一组由四种检测组成的检测方法，以提供 抗凝剂量、肾功能和磷平衡的综合分析。 系统将同时测量抗Xa因子（抗FXa）、活化部分凝血活酶时间（APTT）、血液 从全血中分离出 < 50 µL 的全血输入中的尿素氮 (BUN) 和磷。 （所有四种化验所必需的）将在卡盒上实现自动化，以方便在患者附近进行测试。 结合四种技术复杂的检测（通常发送到实验室的不同部分，例如血液学和 化学）到单个自动化测试中，我们可以减少样品到答案的时间和人员所需的时间 执行每个单独的检测，并且可以显着减少复发所需的累积血液量 CRRT 治疗的整个过程中进行监测。 我们在这个快速通道项目上的合作者包括儿科急性护理肾病学领域的先驱者，他们拥有多个 最近的出版物描述了该项目第一阶段的新方法。 通过开发 DMF 抗 FXa、aPTT、BUN 和磷来验证所提出的测试平台的可行性 第二阶段将结合四种分析方法并展示足够的分析和临床性能。 进入多重反应，得出结果的时间不到 15 分钟，评估分析性能并 每个测定的临床一致性，并对系统进行现场主要用户测试以确定可靠性和 我们的最终产品最初将用于接受 CRRT 的新生儿和儿科患者。 二级市场将包括接受心脏手术或其他手术的儿童和成人患者 与肾衰竭、毒素清除和液体超滤有关。