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: 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
• 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

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 2019年冠状病毒病（COVID-19）是一种呼吸道疾病，使超过700万人患病 在全球范围内，并继续迅速传播。因果病毒，严重的急性呼吸道冠状病毒2（SARS- COV-2），靶向肾脏和急性肾脏损伤是常见的并发症，影响20-40％的住院治疗 患者。肾脏活检和尸检显示出独特的发病机制，包括急性管状损伤 大量数量表明显着的血管内皮损伤和微骨。虽然很高的价格 已经描述了急性肾脏损伤，我们目前尚无关于培养基的数据 COVID-19关于肾功能。潜在的慢性肾脏疾病（CKD）的患者最容易受到伤害 肾脏损伤和子集可能会经历COVID-19之后的快速CKD进展。内皮损伤，这是 在活检和尸检中发现多个受影响器官的重度Covid-19的关键特征可能更多 已经患有影响微脉管系统的肾脏疾病的患者严重且不可逆。 CKD是 Covid-19患者中最常见的合并症之一，目前已经影响 大约5％的美国人口。大量患者的CKD进展 在Covid-19中幸存的疾病将对患者的生活质量产生重大不利影响， 提高发病率和死亡率，并将对美国医疗保健系统大大燃烧。因此，有一个 迫切需要了解Covid-19如何影响EGFR下降，CKD进展的预测因素和 驱动CKD进展后的基本机制，在COVID-19。在AIM 1中，我们将评估 COVID-19，随着估计肾小球滤过率（EGFR）的变化和确定的临床预测因子的变化 与EGFR快速下降相关（由EGFR损失> 25％或肾脏替代疗法的需求定义 持续超过90天）发生在诊断为COVID-19的1年内。阐明这些风险 因素将使我们能够确定Covid-19之后进行性CKD高风险的患者。这个建议 与马萨诸塞州病原体研究中心合作的好处，使我们进入 正在进行的Covid-19患者的生物库中的人类血液样本正在跨多个 马萨诸塞州的地点。在AIM 2中，我们将确定入学的患者的1年肾脏功能结果 该生物库并进行病例对照研究，以确定经历EGFR快速下降的患者是否下降 在感染后的1年内，当时的内皮激活和血液凝结的标记物增加 与具有稳定肾功能的肾功能相比，Covid-19的。该提议的更大目标是建造 初步数据，以准备在接下来的12-24个月内进行R01应用程序，以研究 COVID-19患者的CKD进展。最终，我们希望提高我们对Covid-19的理解 对肾功能的影响并确定干预措施以减少新发行的CKD并发展为终点 幸存者的肾脏疾病。

项目成果

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

• DOI: 10.1016/j.trsl.2021.11.003
• 发表时间: 2022-03
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Long JD;Strohbehn I;Sawtell R;Bhattacharyya R;Sise ME
• 通讯作者: Sise ME

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

• DOI: 10.1016/j.ekir.2021.07.008
• 发表时间: 2021-10
• 期刊: Kidney international reports
• 影响因子: 6
• 作者: Strohbehn IA;Zhao S;Seethapathy H;Lee M;Rusibamayila N;Allegretti AS;Parada XV;Sise ME
• 通讯作者: Sise ME

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: 10.1093/ndt/gfad058
• 发表时间: 2023
• 期刊: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
• 作者: Cho,WonkyungJ;Harden,Destiny;Moreno,Daiana;Dinulos,JamesE;Hanna,PaulE;Wang,Qiyu;Kim,ArthurY;Sise,MeghanE
• 通讯作者: Sise,MeghanE