AKI-Sapere- a novel prognostic of Acute Kidney Injury due to cardiac surgery

AKI-Sapere——心脏手术所致急性肾损伤的新型预后

基本信息

批准号：
10001147
负责人：
Natalia Mitin
金额：
$ 89.32万
依托单位：
SAPERE BIO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001147
关键词：
9p21 Acute Renal Failure with Renal Papillary Necrosis Age Aging Biological Assay Biological Markers CDKN2A gene Cardiac Surgery procedures Cardiovascular Diseases Cardiovascular Surgical Procedures Cell Cycle Cells Characteristics Chronic Kidney Failure Chronology Clinic Clinical Clinical Research Clinical Trials Coronary Artery Bypass Creatinine Critical Illness Cytotoxic Chemotherapy DNA Markers Data Analyses Devices Diagnosis Diagnostic Diagnostic radiologic examination Etiology FDA approved Genetic Predisposition to Disease Healthcare Image Imaging Techniques Individual Injury to Kidney Kidney Kidney Failure Life Experience Logistic Regressions Measurement Measures Medical Imaging Modeling Molecular Morbidity - disease rate Multi-Institutional Clinical Trial Operative Surgical Procedures Organ Transplantation Outcome Patient Care Patient risk Patients Performance Perioperative Pharmacology Phase Pilot Projects Predictive Value Prevention Prevention strategy Procedures Process Prophylactic treatment Protocols documentation Recommendation Regulator Genes Renal dialysis Renal function Research Risk Risk Factors Risk stratification Sensitivity and Specificity Serum Sharps Injury Site Source Supportive care Surgical complication Testing Therapeutic Tissues Validation Work base chemotherapy clinical development clinical practice design healthspan high risk improved in vivo innovation kidney dysfunction meetings molecular marker mortality mutational status novel patient stratification phase 1 study phase 2 study predictive modeling prognostic regenerative renal damage risk minimization risk variant senescence surgical risk tool treatment strategy trial design

项目摘要

ABSTRACT Acute kidney injury (AKI) is common, expensive to treat, and associated with >50% mortality. Each year, millions of patients undergo cardiovascular surgery, medical imaging, or cytotoxic chemotherapy, all of which place them at significant risk for AKI. Around 30% of cardiac surgery patients develop AKI, with even mild AKI significantly increasing the risk of negative outcomes such as progression to chronic kidney disease and 30-day mortality. Although recent research on renal biomarkers has shown promise in diagnosing AKI progression, as yet no tests or models can effectively identify prior to surgery patients at risk for AKI initiation. If patients at risk for developing AKI can be accurately identified before surgery, preoperative and perioperative procedures could be modified to minimize the risk of AKI. Such risk minimization is particularly important since there are no pharmacologic therapies available for the effective prevention or treatment of AKI. Therefore, a clinical tool to predict AKI prior to its initiation remains a critical unmet need. Only through early prediction can clinicians make informed decisions to improve the care of patients at risk of AKI and to limit the burden of this catastrophic complication of surgery and critical illness. By utilizing our novel and robust assay for measuring a patient’s “molecular age”, HealthSpan Dx has developed AKI-Sapere, a multivariate assay that can successfully identify patients at risk for AKI initiation prior to coronary artery bypass graft (CABG) surgery. AKI-Sapere combines measurement of our innovative marker of molecular age along with a DNA marker of genetic predisposition for cardiovascular disease, and a baseline measurement of renal function. In a pilot study of 96 patients undergoing CABG procedures, AKI-Sapere predicted risk of AKI and was superior to AKI risk models composed of clinical variables, such as the Cleveland Clinic Thakar score, or a panel of ten renal biomarkers known to predict AKI progression. In this Fast Track proposal, we propose to conduct multi-center clinical trials to refine the risk score and validate the clinical utility of AKI-Sapere to identify patients at risk for AKI prior to CABG. Completion of these aims will demonstrate the clinical utility of AKI-Sapere in CABG patients and will allow us to bring this test to market, first as a lab developed test (LDT) and ultimately as an FDA-approved device. Prediction of AKI initiation by AKI- Sapere has the potential to dramatically change clinical practice by providing a significantly greater opportunity to intervene, to alter the ensuing renal insult, to council patients and clinicians, and to ultimately diminish the impact of AKI and the associated morbidity on patients and healthcare. Furthermore, use of AKI-Sapere for patient stratification in multiple settings would catalyze the clinical development of novel preventative and treatment strategies for AKI, including potentially AKI caused by sources other than CABG (high-risk surgery, organ transplantation, radiographic imaging and chemotherapy).

抽象的急性肾损伤 (AKI) 很常见，治疗费用昂贵，每年导致数百万人死亡。的患者接受心血管手术、医学成像或细胞毒性化疗，所有这些都使他们大约 30% 的心脏手术患者会出现 AKI，甚至轻度 AKI 也会发生显着风险。增加负面结果的风险，例如进展为慢性肾病和 30 天死亡率。尽管最近关于肾脏生物标志物的研究显示出在诊断 AKI 进展方面的前景，但迄今为止还没有测试或模型可以在手术前有效识别有 AKI 发生风险的患者。可以在手术前准确识别正在发生的 AKI，并可以制定术前和围手术期程序进行修改以尽量减少 AKI 的风险，这种风险最小化尤其重要，因为没有 AKI 风险。可用于有效预防或治疗 AKI 的药物疗法。因此，在 AKI 发生之前预测 AKI 的临床工具仍然是一个尚未满足的关键需求。预测可以做出明智的决定，以改善对 AKI 风险患者的护理并限制通过利用我们新颖而强大的检测方法来减轻这种灾难性手术并发症和危重疾病的负担。 HealthSpan Dx 开发了 AKI-Sapere 来测量患者的“分子年龄”，这是一种多变量检测方法，可以在冠状动脉搭桥术 (CABG) 之前成功识别处于 AKI 起始风险的患者 AKI-Sapere 结合了我们创新的分子年龄标记和 DNA 的测量。心血管疾病遗传易感性的标志，以及肾功能的基线测量。对 96 名接受 CABG 手术的患者进行的试点研究中，AKI-Sapere 预测了 AKI 的风险，并优于由临床变量组成的 AKI 风险模型，例如克利夫兰诊所 Thakar 评分，或一组已知可预测 AKI 进展的十种肾脏生物标志物。在此快速通道提案中，我们建议进行多中心临床试验以细化风险评分并验证 AKI-Sapere 在 CABG 之前识别有 AKI 风险的患者的临床实用性将实现这些目标。展示 AKI-Sapere 在 CABG 患者中的临床效用，并使我们能够首先将该测试推向市场作为实验室开发的测试 (LDT)，并最终作为 FDA 批准的 AKI 引发的预测设备。 Sapere 有潜力通过提供更大的机会来极大地改变临床实践进行干预，改变随后发生的肾脏损伤，向患者和婴儿提供咨询，并最终减少 AKI 及其相关发病率对患者和医疗保健的影响此外，AKI-Sapere 的使用。多种环境下的患者分层将促进新型预防和治疗方法的临床开发 AKI 的治疗策略，包括由 CABG 以外的来源引起的潜在 AKI（高风险手术、器官移植、放射成像和化疗）。