Noninvasive Biomarker Detection of Early Kidney Disease in Patients with Insulin Resistance

胰岛素抵抗患者早期肾脏疾病的无创生物标志物检测

• 批准号: 10323624
• 负责人: AARON L CARRITHERS
• 金额: $ 26.37万
• 依托单位: AMDX PROGNOSTX INCORPORATED
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323624
• 关键词: Acute; Address; Adult; Affect; Age; Archives; Biological Assay; Biological Markers; Blood Glucose; Cardiovascular Diseases; Chemosensitization; Chronic; Chronic Kidney Failure; Clinical; Communities; Contractor; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic tests; Dimensions; Disease; Disease Management; Disease Progression; Early Diagnosis; Early identification; Early treatment; End stage renal failure; Enzyme-Linked Immunosorbent Assay; Epidemic; Erythrocytes; Erythropoiesis; Etiology; Event; Financial Hardship; Functional disorder; Health Care Costs; Healthcare; Healthcare Systems; Human; Hyperglycemia; Hypoxia; Impairment; Individual; Insulin Resistance; International; Intervention; Kidney; Kidney Diseases; Life; Life Expectancy; Link; Measures; Medical; Monoclonal Antibodies; Morbidity - disease rate; Noise; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Pathologic; Pathologic Processes; Patient Care; Patients; Phase; Physicians; Population; Prediabetes syndrome; Prevalence; Preventive treatment; Process; Proteins; Public Health; ROC Curve; Rattus; Reagent; Renal Tissue; Retrospective Studies; Risk; Sampling; Severity of illness; Signal Transduction; Societies; Specificity; Subgroup; Symptoms; Test Result; Testing; Therapeutic Intervention; arteriole; base; cardiovascular risk factor; clinical Diagnosis; clinical decision-making; comorbidity; diabetic; diabetic patient; early detection biomarkers; experience; feasibility testing; high risk; improved; insight; islet amyloid polypeptide; kidney interstitial tissue; mortality; novel marker; patient population; polyclonal antibody; prevent; prototype; renal damage; research and development; scale up; screening; success; tissue injury; treatment planning; validation studies

PROJECT SUMMARY There are over 420 million people living with type 2 diabetes mellitus (T2DM) in the world today and about 165 million also have chronic kidney disease (CKD). The prevalence of CKD is up to 5-fold higher in those with T2DM – in fact, >50% of all T2DM patients will develop CKD in their lifetime. The presence of comorbid CKD in diabetes shortens average life expectancy by ~16-years, and results in ~$250 billion/yr in healthcare costs. Annual mortality rates, manifestation of life-impairing comorbidities like cardiovascular disease, and overall healthcare spending are all greatly increased as CKD severity progresses in T2DM. There is a significant unmet clinical need to identify CKD early in the course of diabetes. Impact of early diagnosis (and proactive implementation of CKD management) in the beginning stages of insulin resistance has been recognized by multiple international societies, yet, no early diagnostic test exists. Prediabetes, the precursor condition to T2DM, currently affects an estimated 88 million U.S. adults, and nearly 90% are unaware of their condition, suggesting that many of these patients are uninhibitedly progressing. While therapeutic intervention is known, proactive medical treatment for every prediabetic patient is impractical since most are low-risk for acutely developing T2DM or kidney disease. Recent findings suggest that a hitherto unclassified pathophysiological process results in rapid progression of prediabetes to T2DM, as well as early development of late-stage CKD. Yet, there is currently no mechanism in place to predict or stratify this “high-risk” subpopulation within prediabetes (that would benefit from early implementation of targeted medical therapy). AMDX PROGNOSTX will produce a new ELISA test that indicates the presence of an ongoing, subclinical pathological process that accelerates T2DM-associated comorbidities and rapid development of irreversible CKD in those with insulin resistance as early as the prediabetic stage. Our test is based on the use of a novel biomarker that reflects critical events in the pathophysiology of CKD progression within this specific prediabetic/early T2DM population. Preliminary results demonstrate that patients with elevated levels of this biomarker either already have, or rapidly develop CKD, and have a particularly high mortality rate. In this Phase I proposal, we will further develop and test our prototype mAb-based assay on longitudinal human samples to evaluate its ability to discern between two populations: i) prediabetic patients who readily developed CKD and T2DM after the onset of their diagnosis, and ii) prediabetic patients who never develop any form of CKD and/or T2DM. Results of this test will offer physicians a new dimension of insight that will redefine the field of diabetes and CKD management and offer advancements in the clinical decision-making process by prompting early medical treatment that will slow, and possibly prevent, progression to late-stage CKD. We request Phase I support to test feasibility of our project and optimize a test that will aid physicians in identifying these high-risk patients in the earliest stages of CKD. Ultimately, we intend to obtain FDA-approval and CMS coverage/reimbursement.

项目摘要 当今世界上有超过4.2亿人患有2型糖尿病（T2DM），约有165人 百万也患有慢性肾脏疾病（CKD）。 CKD的患病率高达5倍 T2DM - 实际上，所有T2DM患者中> 50％的一生将出现CKD。合并CKD的存在 糖尿病将平均预期寿命缩短约16年，医疗保健费用约为2500亿美元。 年死亡率，心血管疾病（如心血管疾病）的合并症的表现以及总体上 随着CKD严重程度在T2DM中的进展，医疗保健支出都大大增加。有重要的 未满足的临床需要在糖尿病过程中识别CKD。早期诊断（主动）的影响 在胰岛素抵抗的开始阶段，CKD管理的实施已得到认可 但是，多个国际社会尚无早期诊断测试。前糖尿病，前体条件 T2DM目前影响约8800万美国成年人，几乎90％的人没有意识到自己的状况， 这表明许多患者没有避免进展。虽然已知治疗干预措施，但 每位糖尿病前患者的主动医疗治疗都是不切实际的 发展T2DM或肾脏疾病。最近的发现表明迄今未分类的病理生理学 过程导致糖尿病前期到T2DM的快速发展，以及晚期CKD的早期发展。 但是，目前尚无预测或分层此“高风险”亚群的机制 前糖尿病（这将受益于靶向药物治疗的早期实施）。 AMDX PROGNOSTX将 产生新的ELISA测试，表明存在持续的亚临床病理过程 这加速了T2DM相关的合并症和不可逆CKD的快速发展 早在糖尿病前期就具有胰岛素抵抗。我们的测试基于新型生物标志物的使用 这反映了CKD进展的病理生理学中的关键事件 T2DM人口。初步结果表明，该生物标志物水平升高的患者 已经有或迅速发展CKD，并具有特别高的死亡率。在这个阶段我的建议中，我们 将进一步开发和测试我们对纵向人类样品的基于mAb的原型测定法，以评估其 能够辨别两个人群的能力：i）糖尿病前患者，这些患者很容易开发CKD和T2DM 其诊断的发作以及II）从未形式的CKD和/或T2DM的糖尿病前患者。 该测试的结果将为医生提供一个新的见解方面，该方面将重新定义糖尿病领域和 CKD管理并通过提示早期医疗来提供临床决策过程中的进步 可以放慢并可能预防晚期CKD的治疗。我们要求我支持阶段 测试我们项目的可行性并优化一项测试，该测试将有助于医生确定这些高风险患者 CKD最早的阶段。最终，我们打算获得FDA批准和CMS覆盖范围/报销。