Low cost quantitative monitoring of kidney injury biomarkers using a glucometer

使用血糖仪对肾损伤生物标志物进行低成本定量监测

• 批准号: 8591630
• 负责人: Tian Lan
• 金额: $ 13.68万
• 依托单位: GLUCOSENTIENT, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591630
• 关键词: Acute; Address; Allografting; Animal Model; Antibodies; Binding; Biochemical; Biological Assay; Biological Markers; Biopsy; Buffers; Clinical; Collaborations; Complex; Country; Creatinine; Detection; Development; Devices; Dialysis procedure; Enzymes; Evaluation; Failure; Foundations; Functional disorder; Future; Gelatinase A; Generations; Glomerular Filtration Rate; Glucose; Goals; Gold; Health; Health Care Costs; Histology; Hour; Illinois; Immunosuppressive Agents; Information Systems; Injury; Interleukin-18; Invertase; Kidney; Kidney Failure; Kidney Transplantation; Laboratories; Licensing; Literature; Marketing; Measures; Methods; Monitor; Organ; Outcome; Outcome Assessment; Pathologist; Patients; Phase; Procedures; Process; Proteins; Proteinuria; Publishing; Quality of life; Reader; Recovery; Renal function; Research; Risk; Sampling; Sampling Errors; Severities; Signal Transduction; Site; Small Business Innovation Research Grant; Solutions; Sucrose; Surface; System; Technology; Testing; Therapeutic Intervention; Tissue Sample; Transplant Recipients; Transplantation; Universities; Urine; Validation; Work; antibody conjugate; assay development; base; cost; delayed graft function; design; diabetic patient; economic impact; experience; functional group; glucose production; graft failure; graft function; health economics; improved; innovation; innovative technologies; magnetic beads; monitoring device; point of care; prototype; public health relevance; rat KIM-1 protein; sensor

DESCRIPTION (provided by applicant): While the high costs of healthcare in the U.S. can be felt by everyone in the country, the economic impact to patients with kidney failure is particularl significant as dialysis treatments can reach $85,000 annually, with transplantation being the only known cure. Therefore, kidney transplants today make up more than half of all transplants performed in the U.S., with roughly 17,000 transplants every year. Unfortunately, up to 29% of kidney failure rate is observed for a subset of these transplant patients and delayed graft function also occur in 23% of these kidney recipients. To address this issue, powerful immunosuppressant therapies have been developed to reduce the chances of transplant complications, but such therapies may not be necessary or appropriate for all patients. Therefore, early warning of graft failure has a significant positive economic and health impact by allowing earlier, less intensive, and more effective therapeutic intervention. The current standard practice for evaluating kidney function is through an invasive renal biopsy. Unfortunately, the process of removing a tiny, random tissue sample from patient's kidney leads to significant sampling errors; moreover, the histological evaluation of the biopsies is subjective and can vary amongst pathologists or even the same pathologist reviewing biopsies from opposite poles of the same kidney. Biomarkers such as creatinine, glomerular filtration rate, and proteinuria have also been used for evaluating kidney function; however, they are limited in their prediction power. Among several potential biomarkers for kidney injury, Kidney Injury Molecule-1 (Kim-1) is well studied in the clinical setting and in the animal model. Kim-1 is shed into urine as a soluble form and it is stable for up to 24 hours, therefore its detection in urine is not invasive. In some instance, Kim-1 is more sensitive than histology for allograft injury. Clinical laboratory tests are available for quantifying Kim-1 in the urine as well as a dipstick test that cn qualitatively detect the presence of Kim-1. Neither test, however, allows for routine quantification of Kim-1 levels at a reasonable cost; being able to monitor the Kim-1 level quantitatively allows the potential for identifying the severity of kidney injury, risk stratificaton of patients in clinical setting, to guide therapy and determine if kidney injury is improving or gettig worse. Towards this goal, GlucoSentient is developing a quantitative monitoring device for Kim-1 that is effective, affordable, and easy to use. We can achieve this goal by developing assays for biomarkers for kidney injury, with Kim-1 as the initial target, to be used with existing glucometers, which are based on low-cost, easy to construct electrochemical sensors. By combining the gold standard antibody based assay with low cost detection technology, GlucoSentient will develop a final product that allows post-kidney-transplant patients to monitor their kidney function by frequently measuring Kim-1 in urine. We believe this product can greatly increase the quality of life for post-transplant patient as well as reduce the associated costs for kidney failure and dysfunction.

描述（由申请人提供）：虽然美国的医疗保健费用很高，但对肾衰竭患者的经济影响尤其显著，因为透析治疗每年可达到85，000美元，移植是唯一已知的治疗方法。因此，今天的肾移植占美国所有移植手术的一半以上，每年大约有17,000例移植手术不幸的是，在这些移植患者的一个子集中观察到高达29%的肾衰竭率，并且在这些肾接受者中的23%中也发生移植物功能延迟。为了解决这个问题，已经开发了强大的免疫抑制剂疗法来减少移植并发症的机会，但这种疗法可能不是所有患者都需要或适合的。因此，移植失败的早期预警通过允许更早、更少强度和更有效的治疗干预具有显著的积极经济和健康影响。 目前评价肾功能的标准做法是通过侵入性肾活检。不幸的是，从患者肾脏中取出微小的随机组织样本的过程会导致显著的采样错误;此外，活检的组织学评估是主观的 并且可以在病理学家之间变化，甚至在同一病理学家之间变化，所述病理学家从同一肾脏的相反两极检查活检。生物标志物如肌酐、肾小球滤过率和蛋白尿也被用于评估肾功能;然而，它们的预测能力有限。在肾损伤的几种潜在生物标志物中，肾损伤分子-1（Kim-1）在临床环境和动物模型中得到了充分研究。Kim-1在尿液中脱落 作为可溶形式，其稳定长达24小时，因此其在尿液中的检测是非侵入性的。在某些情况下，Kim-1对同种异体移植物损伤比组织学更敏感。 临床实验室测试可用于定量尿液中的Kim-1以及可定性检测Kim-1存在的试纸测试。然而，这两种测试都不允许以合理的成本对Kim-1水平进行常规定量;能够定量监测Kim-1水平允许识别肾损伤的严重程度、临床环境中患者的风险分层的潜力，以指导治疗并确定肾损伤是否正在改善或变得更糟。为了实现这一目标，GlucoSentient正在为Kim-1开发一种有效、经济实惠且易于使用的定量监测设备。我们可以通过开发用于肾损伤的生物标志物的测定来实现这一目标，以Kim-1为初始靶标，与现有的血糖仪一起使用，这些血糖仪基于低成本，易于构建的电化学传感器。通过将基于金标准抗体的检测与低成本检测技术相结合，GlucoSentient将开发出一种最终产品，使肾移植后的患者能够通过频繁测量尿液中的Kim-1来监测他们的肾功能。我们相信这种产品可以大大提高移植后患者的生活质量，并降低相关的费用， 肾衰竭和功能障碍。