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).

抽象的急性肾脏损伤（AKI）很常见，治疗昂贵，并且与50％的死亡率有关。每年，数百万患者接受心血管手术，医学成像或细胞毒性化学疗法，所有这些都将其放置有很大的AKI风险。大约30％的心脏手术患者患有AKI，甚至有明显的AKI 增加了负面结果的风险，例如慢性肾脏疾病和30天死亡率的进展。尽管最近对肾脏生物标志物的研究在诊断性AKI进展方面表现出了希望，但尚未测试或模型可以在有AKI倡议风险的手术患者之前有效识别。如果患者有风险可以在手术前准确识别出AKI，术前和周期性的程序可能是修改以最大程度地减少AKI的风险。这种风险最小化特别重要，因为没有可用于有效预防或治疗AKI的药物疗法。因此，在AKI计划之前预测AKI的临床工具仍然是一个至关重要的未满足需求。只能通过早期预测临床医生可以做出明智的决定，以改善有AKI风险的患者的护理，并限制这种灾难性手术和重症疾病并发症的负担。通过使用我们的小说和强大的测定法 HealthSpan DX测量患者的“分子年龄”，开发了Aki-Sapere，这是一种多元测定法可以在冠状动脉旁路移植物（CABG）之前成功识别有AKI倡议风险的患者外科手术。 Aki-Sapere结合了我们的分子年龄创新标记和DNA的测量心血管疾病的遗传易感性标记，以及肾功能的基线测量。在对96名接受CABG手术的患者的试点研究，AKI-SAPERE预测了AKI的风险，为优于由临床变量组成的AKI风险模型，例如Cleveland Clinic Thakar评分，或已知可以预测AKI进展的十个肾脏生物标志物。在这个快速提议中，我们建议进行多中心临床试验以完善风险评分并验证 AKI-Sapere的临床实用性是在CABG之前识别有AKI风险的患者。这些目标的完成将展示Aki-Sapere在CABG患者中的临床实用性，并将使我们能够将该测试推向市场，首先作为实验室开发的测试（LDT），最终是FDA批准的设备。 Aki对AKI倡议的预测 Sapere可以通过提供更大的机会来大大改变临床实践干预，改变确保肾脏伤害，对理事会患者和临床医生，并最终减少 AKI和相关的发病率对患者和医疗保健的影响。此外，使用Aki-Sapere 在多种环境中的患者分层会催化新型预防性的临床发展和 AKI的治疗策略，包括由CABG以外的其他来源引起的AKI（高风险手术，器官移植，射线照相成像和化学疗法）。