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.

项目总结