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.

摘要 用于连续肾移植期间反复抗凝和肾脏监测的低血容量平台 危重患儿的替代治疗 （快速通道SBIR PA-20-260） 急性肾损伤（阿基）的特征在于肾脏充分地维持肾脏功能的能力突然下降。 维持电解质、酸碱和液体平衡。高达30%的重症监护室收治的儿童 阿基和阿基的存在与住院时间延长和更高的 死亡率。连续性肾脏替代治疗（CRRT）已成为首选透析方式 对于重症儿童，新生儿和幼儿（10公斤以下）越来越常见， 阿基和先天性肾衰竭。频繁监测（每天2-6次）抗凝治疗（肝素， 类肝素等），肾功能（尿素）和电解质成分（钾、磷等）要 在CRRT过程中。现有的实验室测试需要大量的血液，累积失血量 会导致医源性贫血大多数危重新生儿（90%的极重度新生儿） 低出生体重儿和58%的早产儿）在出生后需要输注红细胞。 新生儿重症监护室（NICU）由于频繁抽血。 为了满足新生儿和儿童CRRT监测中快速、低容量血液检测的关键未满足需求， 我们将在我们的近患者数字微流控（DMF）平台上开发一组四种检测方法， 抗凝剂量、肾功能和磷平衡的综合分析。我们的创新 系统将同时测量抗凝血因子Xa（抗FXa）、活化部分凝血活酶时间（aPTT）、血液 尿素氮（BUN）和来自< 50 µL全血输入的磷。从全血中分离血浆 （所有四种测定所需）将在检测盒上自动化，以便于在患者附近进行检测。通过 将四种技术上复杂的测定（通常发送到实验室的不同部分，例如血液学和 化学）到一个单一的自动化测试，我们可以减少样品的时间，以回答和人员所需的时间， 进行每一个单独的测定，并可以显着减少所需的血液的累积体积复发 在CRRT治疗的整个过程中进行监测。 我们在这个快速通道项目中的合作者包括儿科急性护理肾脏病学的先驱， 描述新生儿CRRT新方法的近期出版物。该项目的第一阶段将建立 通过开发DMF抗FXa、aPTT、BUN和磷，确定拟定试验平台的可行性 分析和证明充分的分析和临床性能。第二阶段将联合收割机结合四种检测 在15分钟内获得结果的多重反应中，评价分析性能， 每个检测试剂盒的临床一致性，并对系统进行现场主要用户测试，以确定可靠性， 可用性我们的最终产品最初将上市用于接受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科和成人患者 与肾衰竭、毒素清除和液体超滤相关。