Novel Saliva-based Renal Function Test Platform

新型唾液肾功能检测平台

• 批准号: 9789463
• 负责人: Manal Beshay
• 金额: $ 73.72万
• 依托单位: INTELLIGENT OPTICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789463
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adult; Affect; Agreement; Biological Assay; Biological Markers; Blood; Blood specimen; Businesses; Calibration; California; Caring; Case Study; Cessation of life; Characteristics; Chemistry; Child; Chronic Kidney Failure; Clinic; Clinical; Clinical Trials; Collaborations; Complex; Creatinine; Data; Detection; Deterioration; Developing Countries; Development; Device or Instrument Development; Devices; Disease Progression; Dose; Ensure; Enzymes; Event; Filtration; Fluorescent Dyes; Goals; Gold; Graft Rejection; Home environment; Human; Intelligence; Intelligence Tests; Kidney; Kidney Diseases; Kidney Transplantation; Laboratories; Lateral; Measurable; Measurement; Measures; Medical; Methods; Monitor; Nephrology; Optics; Patient Monitoring; Patient-Focused Outcomes; Patients; Periodicity; Periodontal Diseases; Phase; Population; Protocols documentation; Reagent; Renal function; Reporting; Reproducibility; Research; Saliva; Salivary; Sampling; San Francisco; Serum; Serum Markers; Specificity; Specimen Handling; Statistical Data Interpretation; Structure; Substance Abuse Detection; Supervision; System; Techniques; Technology; Testing; Time; Translating; Transplant Recipients; Transplantation; Underserved Population; Universities; Urea; Validation; Venous blood sampling; Visit; analog; assay development; base; blind; bone metabolism; care outcomes; clinical application; clinically relevant; commercialization; cost effective; cross reactivity; design; human subject; improved; innovation; instrument; novel; phase 2 study; phase 2 testing; point of care; portability; post gamma-globulins; rapid technique; remote location; response; salivary assay; screening; tool; transplant centers; urgent care

Project Summary Chronic Kidney Disease (CKD) affects millions of people worldwide, including 20 million adults and children in the USA. Timely detection of kidney function deterioration can improve management of CKD, including in kidney transplanted recipients. Without a blood draw, an acute kidney injury (AKI) event or a transplant rejection could remain unrecognized for extended periods of time, leading to irreversible loss of kidney function and structure. Novel patient-friendly methods of kidney function measurement with high levels of precision and reproducibility are urgently needed to ensure more frequent and reliable monitoring in the home and for point-of-care screening. Currently, invasive phlebotomy followed by laborious blood specimen processing and reporting are the only way to measure the three major kidney filtration markers: serum creatinine, urea, and cystatin C. However, saliva has been proven to mirror blood biomarker levels. Limited preliminary data suggest that salivary creatinine and urea levels correlate with those in serum in CKD patients. Measurable levels of cystatin C have been assayed in saliva without being affected by periodontal disease. Based on these findings, Intelligent Optical Systems (IOS), in collaboration with the University of California (UC) Irvine and UC San Francisco, plans to develop (Phase I, 12 months) a novel means of detecting creatinine, cystatin C, and urea in saliva, using a highly sensitive and selective enzyme-based lateral flow assay (ELF assay). In this novel, compact, single-step, enzymatic multiplexed assay, highly fluorescent dyes yield reliable quantitative measurements on a portable analyzer. The innovatively developed methods will be subsequently (Fast-Track) validated in 200 CKD patients from UCI nephrology and transplant clinics (Phase II, 24 months). The proposed development builds on extensive IOS expertise in complex assay development, using saliva matrix that has been successfully validated in clinics for bone metabolism markers and rapid testing for drug of abuse. In Phase I we will demonstrate the feasibility of recording reproducible and sensitive measurements of salivary creatinine, cystatin C, and urea, using spiked and laboratory tested human saliva samples obtained from BioreclamationIVT. Assay specification, sensitivity LOD, specificity, and stability will be reported by the end of Phase I in accordance with IOS-established protocols for salivary assay development and optimization. Building on a successful Phase I demonstration of an ELF assay, and validating the results against the predetermined milestone criteria, we will then conduct the clinical validation in Phase II, testing saliva measurements against blood levels in 200 human subjects with CKD – including 50 kidney transplant recipients – with a broad range of GFR of 10-60 mL/min/1.73 m2 BSA. Our proposed Fast-Track design is efficient, feasible, and innovative, and has a high likelihood of sustained powerful influence and immediate clinical applicability. The availability of non-invasive, point-of-care, multiplex measures of kidney function would have a dramatic impact on the care and monitoring of patients with CKD, particularly in remote locations.

项目摘要 慢性肾病（CKD）影响着全球数百万人，其中包括2000万成人和儿童。 美国.及时检测肾功能恶化可以改善CKD的管理，包括肾脏 移植受体如果不抽血，急性肾损伤（阿基）事件或移植排斥反应可能 长期未被发现，导致肾功能和结构的不可逆损失。 新的患者友好型肾功能测量方法，具有高水平的精确度和重现性 以确保更频繁和可靠的家庭监测和护理点筛查。 目前，侵入性静脉切开术，然后是费力的血液标本处理和报告是唯一的方法 测量三种主要的肾脏滤过标志物：血清肌酐、尿素和胱抑素C。然而，唾液 已经被证明可以反映血液生物标志物水平。有限的初步数据表明，唾液肌酐和尿素 与CKD患者血清中的水平相关。已测定了可测量水平的胱抑素C， 牙周病的危害有哪些？基于这些发现，智能光学系统（IOS）， 与加州大学（UC）欧文分校和加州大学旧金山分校弗朗西斯科合作，计划开发（第一阶段， 12个月）的一种新的手段，检测肌酸酐，胱抑素C，和尿素在唾液中，使用高灵敏度， 选择性酶基侧向流测定（ELF测定）。在这种新颖的，紧凑的，单步的，酶促的 多路检测，高荧光染料产生可靠的定量测量便携式分析仪。的 随后将在来自UCI的200例CKD患者中验证创新开发的方法（快速通道） 肾脏病学和移植诊所（第二阶段，24个月）。拟议的发展以广泛的内部监督事务厅为基础， 在复杂检测开发方面的专业知识，使用唾液基质，已在临床上成功验证， 骨代谢标志物和滥用药物的快速检测。在第一阶段，我们将证明 记录唾液肌酐、半胱氨酸蛋白酶抑制剂C和尿素的可重复和灵敏的测量，使用加标的 和从BioreclamationIVT获得的实验室测试的人唾液样品。测定质量标准，灵敏度 根据IOS制定的方案，将在I期结束时报告LOD、专属性和稳定性 用于唾液检测开发和优化。在ELF第一阶段成功示范的基础上 检测，并根据预定的里程碑标准验证结果，然后我们将进行临床 在第二阶段的验证，测试唾液测量对血液水平在200名人类受试者与CKD - 包括50名肾移植受者-GFR范围为10-60 mL/min/1.73 m2 BSA。我们 拟议的快速通道设计是有效的，可行的，创新的，并有很高的可能性，持续强大的 影响和直接临床应用。无创、即时、多重措施的可用性 肾功能的改善将对CKD患者的护理和监测产生巨大影响，特别是在 偏远地区。