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 并在全球范围内继续迅速传播。致病病毒是严重急性呼吸道冠状病毒 2 型（SARS- 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。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 大量数据显示明显的血管内皮损伤和微血栓。虽然利率高 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。患有潜在慢性肾脏病 (CKD) 的患者最容易受到 肾损伤，并且一部分人可能会在 COVID-19 后经历快速的 CKD 进展。内皮损伤，即 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。慢性肾病是 COVID-19 患者最常见的合并症之一，目前已影响到 约占美国人口的5%。大量患者的 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，并将给美国医疗保健系统带来巨大负担。因此，有一个 迫切需要了解 COVID-19 如何影响 eGFR 下降、CKD 进展的预测因素以及 COVID-19 后驱动 CKD 进展的潜在机制。在目标 1 中，我们将评估以下关联： 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。对这些风险的说明 这些因素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。这个提议 受益于与马萨诸塞州病原体研究中心的合作，使我们能够获得 人类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 马萨诸塞州的站点。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 与肾功能稳定的患者相比，COVID-19 的发生情况。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 COVID-19 患者的 CKD 进展。最终，我们希望加深对 COVID-19 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

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