Effect of Covid-19 on chronic kidney disease progression

Covid-19 对慢性肾脏病进展的影响

• 批准号: 10194834
• 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
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-04 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194834
• 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 pandemic; COVID-19 patient; COVID-19 severity; 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; Long-Term Effects; 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; 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 population; experience; flexibility; hazard; high risk; improved; kidney biopsy; kidney dysfunction; 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

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.

项目摘要 冠状病毒病2019(新冠肺炎)是一种呼吸系统疾病，已使700多万人患病 在全球范围内，并继续迅速传播。致病病毒，严重急性呼吸道冠状病毒2(SARS- CoV-2)，靶向肾脏，急性肾损伤是一种常见的并发症，影响20%-40%的住院患者 病人。肾脏活检和尸检显示一种独特的发病机制，包括急性肾小管损伤和 大量患者显示明显的血管内皮细胞损伤和微血栓。虽然利率很高 关于急性肾损伤的研究，我们目前还没有中长期影响的数据。 新冠肺炎对肾功能的影响。基础慢性肾脏病(CKD)患者最容易患上 肾脏损伤，新冠肺炎后一部分患者可能经历快速的慢性肾脏病进展。内皮损伤，这是 在多个受累器官的活检和尸检中发现的严重新冠肺炎的一个关键特征可能是 对于已经患有影响微血管系统的肾脏疾病的患者，这是严重的和不可逆转的。CKD是 新冠肺炎患者最常见的并发症之一，目前已影响到 约占美国人口的5%。大量慢性肾脏病患者病情进展加速 新冠肺炎患者存活的既往疾病将对患者的生活质量产生实质性的不利影响， 增加发病率和死亡率，并将成为美国医疗体系的一大负担。因此，有一个 迫切需要了解新冠肺炎如何影响表皮生长因子受体的下降，慢性肾脏病进展的预测因素，以及 新冠肺炎后慢性肾脏病进展的潜在机制。在目标1中，我们将评估 新冠肺炎与估计的肾小球滤过率的变化并确定临床预测因子 与EGFR快速下降有关(定义为EGFR丢失25%或需要肾脏替代治疗 持续90天以上)，发生在新冠肺炎确诊后1年内。对这些风险的解释 这些因素将使我们能够识别新冠肺炎术后进展性慢性肾功能不全的高危患者。这项建议 受益于与马萨诸塞州病原体研究中心的合作，使我们能够访问 来自正在进行的新冠肺炎患者生物库的人体血液样本，该库正在登记多个 马萨诸塞州的网站。在目标2中，我们将确定登记的患者的1年肾功能结果。 该生物库并进行病例对照研究以确定经历快速EGFR下降的患者 在感染后1年内有内皮激活和凝血标志物增加的时候 与肾功能稳定的人相比，新冠肺炎的患者更容易患上糖尿病。这项提议的更大目标是建立 在未来12-24个月内为R01应用做准备的初步数据，以研究 新冠肺炎患者的慢性肾脏病进展情况。最终，我们希望提高对新冠肺炎的S的理解 对肾功能的影响和确定减少新发CKD和进展到终末期的干预措施 幸存者的肾脏疾病。