Effect of Covid-19 on chronic kidney disease progression

项目摘要 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 在世界范围内迅速蔓延。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， 患者肾活检和尸检显示了独特的发病机制，包括急性肾小管损伤， 显著的数量表明显著的血管内皮损伤和微血栓。虽然高利率 急性肾损伤的描述，我们目前还没有中期至长期影响的数据， COVID-19对肾功能的影响。患有基础慢性肾病（CKD）的患者最容易受到 肾损伤，并且一个子集可能在COVID-19后经历快速CKD进展。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， 在已经患有影响微血管系统的肾脏疾病的患者中是严重的和不可逆的。CKD是 COVID-19患者中最常见的合并症之一，目前已影响 约占美国人口的5%。在大量CKD患者中， 从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，并将成为美国医疗保健系统的巨大负担。因此有 迫切需要了解COVID-19如何影响eGFR下降，CKD进展的预测因素， COVID-19后推动CKD进展的潜在机制。在目标1中，我们将评估 COVID-19与估计肾小球滤过率（eGFR）的变化，并确定临床预测因素， 与eGFR快速下降（定义为eGFR损失> 25%或需要肾脏替代治疗）相关 持续超过90天），在确诊COVID-19后1年内发生。阐明这些风险 这些因素将使我们能够识别COVID-19后进展性CKD的高风险患者。这项建议 得益于与马萨诸塞州病原体研究中心的合作， 来自正在进行的COVID-19患者生物库的人类血液样本，该生物库正在招募多个 马萨诸塞州的一个地点。在目标2中，我们将确定入组研究的患者的1年肾功能结局。 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 在感染后1年内，内皮活化和血液凝固的标志物增加， 与肾功能稳定的人相比，COVID-19的发病率更高。该提案的更大目标是建立 在未来12-24个月内为R 01申请做准备的初步数据， 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CKD和进展到终末期 幸存者的肾脏疾病。

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.