Effect of Covid-19 on chronic kidney disease progression

Covid-19 对慢性肾脏病进展的影响

基本信息

批准号：
10341216
负责人：
Meghan E. Sise
金额：
$ 12.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-04 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10341216
关键词：
2019-nCoV Acute Acute Kidney Tubular Necrosis Acute Renal Failure with Renal Papillary Necrosis Adult Adverse effects Affect Age Angiopoietin-2 Automobile Driving Autopsy Biological Markers Biopsy Blood Vessels Blood coagulation Blood specimen Boston COVID-19 COVID-19 diagnosis COVID-19 impact COVID-19 pandemic COVID-19 patient COVID-19 severity COVID-19 survivors Case-Control Studies Cell Adhesion Molecules Chronic Kidney Failure Collaborations Complication Coronavirus Creatinine Data Disease Disease Outcome Disease Progression End stage renal failure Endothelium Enrollment Ethnic Origin Fibrin fragment D Functional disorder Future Gender Glomerular Filtration Rate Goals Health Healthcare Systems Hospitals Human ICAM1 gene Immunophenotyping Infection Injury Injury to Kidney Institutes Intervention Kidney Kidney Diseases Lead Letters Literature Manuscripts Massachusetts Measures Mentored Patient-Oriented Research Career Development Award Modeling Morbidity - disease rate Nephrology Organ Outcome Pathogenesis Pathway interactions Patients Peripheral Blood Mononuclear Cell Persons Plasma Population Predictive Value Preparation Proteinuria Proteomics Quality of life Race Renal Replacement Therapy Renal function Research Retrospective cohort study Risk Risk Factors Role SARS-CoV-2 infection Sampling Scientist Severity of illness Site Survival Analysis Survivors Testing Time Tubular formation Urine Vascular Endothelial Growth Factors Vascular Endothelium Viral Virus Virus Diseases Work biobank career clinical care clinical predictors clinically significant cohort comorbidity ethnic minority experience flexibility hazard high risk improved kidney biopsy kidney dysfunction long term consequences of COVID-19 mortality pandemic disease pathogen patient population predictive modeling programs racial minority rate of change repository respiratory severe COVID-19 skills translational scientist von Willebrand Factor

项目摘要

Project Summary Coronavirus disease 2019 (COVID-19) is a respiratory illness that has sickened over 7 million people worldwide and continues to rapidly spread. The causal virus, severe acute respiratory coronavirus 2 (SARS- CoV-2), targets the kidney, and acute kidney injury is a common complication, affecting 20-40% of hospitalized patients. Kidney biopsies and autopsies show a unique pathogenesis including acute tubular injury with significant numbers demonstrating prominent vascular endothelial injury and microthrombi. Although high rates of acute kidney injury have been described, we currently have no data on the medium to long-term effects of COVID-19 on kidney function. Patients with underlying chronic kidney disease (CKD) are most vulnerable to kidney injury, and a subset may experience rapid CKD progression after COVID-19. Endothelial injury, which is a key feature of severe COVID-19 found on biopsies and autopsies of multiple affected organs, may be more severe and irreversible in patients who already have kidney diseases that affect the microvasculature. CKD is one of the most common comorbidities among patients with COVID-19, which has currently affected approximately 5% of the US population. Accelerated CKD progression in a large number of patients with preexisting illness who survive COVID-19 will have a substantial adverse effect on patients’ quality of life, increase morbidity and mortality, and will be a large burden to the US healthcare system. Therefore, there is a pressing need to understand how COVID-19 affects eGFR decline, predictors of CKD progression, and underlying mechanisms driving CKD progression after COVID-19. In Aim 1, we will evaluate the association of COVID-19 with changes in estimated glomerular filtration rate (eGFR) and determine clinical predictors that are associated with rapid eGFR decline (defined by > 25% loss of eGFR or need for renal replacement therapy lasting more than 90 days) occurring within 1 year after diagnosis of COVID-19. Elucidation of these risk factors will allow us to identify patients who are at high risk of progressive CKD after COVID-19. This proposal benefits from collaboration with the Massachusetts Center for Pathogen Research, allowing us access to human blood samples from an ongoing biobank of patients with COVID-19 that is enrolling across multiple sites in Massachusetts. In Aim 2, we will determine 1-year kidney function outcomes in the patients enrolled in this biobank and perform a case-control study to determine if patients who experience rapid eGFR decline within 1 year after infection have increased markers of endothelial activation and blood coagulation at the time of COVID-19 compared to those with stable kidney function. The larger goal of this proposal is to build preliminary data in preparation for an R01 application over the next 12-24 months to study mechanisms of CKD progression in patients with COVID-19. Ultimately, we hope to improve our understanding of COVID-19’s effect on kidney function and identify interventions to decrease new-onset CKD and progression to end-stage renal disease in survivors.

项目概要 2019 年冠状病毒病 (COVID-19) 是一种呼吸道疾病，已导致超过 700 万人患病致病病毒——严重急性呼吸道冠状病毒 2（SARS-）在全球范围内持续迅速传播。 CoV-2），以肾脏为目标，急性肾损伤是一种常见并发症，影响 20-40% 的住院患者患者的肾脏活检和尸检显示出独特的发病机制，包括急性肾小管损伤。尽管发生率很高，但大量数据表明存在明显的血管内皮损伤和微血栓。急性肾损伤的影响已经被描述，我们目前没有关于中长期影响的数据 COVID-19 对肾功能的影响。患有潜在慢性肾病 (CKD) 的患者最容易受到感染。肾损伤，并且一部分可能会在 COVID-19 后经历快速的 CKD 进展，即内皮损伤。在多个受影响器官的活检和尸检中发现的严重 COVID-19 的一个关键特征可能是对于已经患有影响微血管的肾脏疾病的患者来说，这是严重且不可逆转的。 COVID-19 患者最常见的合并症之一，目前已影响到大约 5% 的美国人口患有慢性肾病 (CKD) 进展加速。在 COVID-19 中幸存下来的既存疾病将对患者的生活质量产生重大不利影响，增加发病率和死亡率，并将给美国医疗系统带来巨大负担。迫切需要了解 COVID-19 如何影响 eGFR 下降、CKD 进展的预测因素以及在目标 1 中，我们将评估 COVID-19 后驱动 CKD 进展的潜在机制。 COVID-19 与估计肾小球滤过率 (eGFR) 的变化并确定临床预测因子与 eGFR 快速下降相关（定义为 eGFR 下降 > 25% 或需要肾脏替代治疗持续超过 90 天）发生在诊断出 COVID-19 后 1 年内。该提案将使我们能够识别出在 COVID-19 后处于进展性 CKD 高风险的患者。受益于与马萨诸塞州病原体研究中心的合作，使我们能够获得人体血液样本来自正在开展的 COVID-19 患者生物库，该生物库正在多个国家/地区进行招募在目标 2 中，我们将确定入组患者的 1 年肾功能结果。该生物库并进行病例对照研究，以确定患者是否经历过 eGFR 快速下降感染后 1 年内，当时的内皮活化和凝血标志物增加与那些肾功能稳定的人相比，该提案的更大目标是建立。为未来 12-24 个月的 R01 申请做准备以研究机制的初步数据最终，我们希望加深对 COVID-19 患者的 CKD 进展的了解。对肾功能的影响并确定干预措施以减少新发 CKD 和进展至终末期幸存者的肾脏疾病。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Oral antiviral therapies for COVID-19 in patients with advanced chronic kidney disease or kidney failure.

针对晚期慢性肾病或肾衰竭患者的 COVID-19 口服抗病毒疗法。

DOI：
发表时间：
2023-07-31
期刊：
影响因子：
0
作者：
Cho, Wonkyung J;Harden, Destiny;Moreno, Daiana;Dinulos, James E;Hanna, Paul E;Wang, Qiyu;Kim, Arthur Y;Sise, Meghan E
通讯作者：
Sise, Meghan E

COVID-19 Survival and its impact on chronic kidney disease.

COVID-19 生存及其对慢性肾脏病的影响。

DOI：
发表时间：
2022-03
期刊：
影响因子：
0
作者：
Long, Joshua D;Strohbehn, Ian;Sawtell, Rani;Bhattacharyya, Roby;Sise, Meghan E
通讯作者：
Sise, Meghan E

Acute Kidney Injury Incidence, Recovery, and Long-term Kidney Outcomes Among Hospitalized Patients With COVID-19 and Influenza.

COVID-19 和流感住院患者的急性肾损伤发生率、恢复和长期肾脏结果。

DOI：
发表时间：
2021-10
期刊：
影响因子：
6
作者：
Strohbehn, Ian A;Zhao, Sophia;Seethapathy, Harish;Lee, Meghan;Rusibamayila, Nifasha;Allegretti, Andrew S;Parada, Xavier Vela;Sise, Meghan E
通讯作者：
Sise, Meghan E