Role of Kidney Proximal Tubular Secretion in Critical Illness

肾近端肾小管分泌在危重疾病中的作用

基本信息

批准号：
10217335
负责人：
BRYAN R KESTENBAUM
金额：
$ 50万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217335
关键词：
2019-nCoV Acute Acute Renal Failure with Renal Papillary Necrosis Address Adult Adult Respiratory Distress Syndrome Amino Acids Aminopeptidase Angiotensin Receptor Angiotensins Arginine Autopsy Binding Proteins Biological Biological Assay COVID-19 Case Series Catalogs Cell surface Cells Cessation of life Citrulline Clinical Clinical Data Clinical assessments Coupled Creatinine Critical Illness Disease Distal Dose Endothelial Cells Enrollment Epidermal Growth Factor Epithelial Cells Failure Filtration Functional disorder Funding Goals Grant Hormones Hospitalization Hypoxemia Immune response Impairment Incidence Individual Inflammatory Injury Injury to Kidney Kidney Knowledge LCN2 gene Measurement Measures Mediating National Institute of Diabetes and Digestive and Kidney Diseases Outcome Parents Pathogenesis Pathologic Pathway interactions Patients Pattern Peptidyl-Dipeptidase A Persons Pharmaceutical Preparations Phase Physiological Plasma Process Prospective Studies Prospective cohort Prospective cohort study Protein Secretion Renal function Renal tubule structure Reporting Role Serum Severities Severity of illness System Testing Thrombosis Time Tubular formation Viral base biomarker development cell type clinically significant cohort comparison group drug synthesis endothelial dysfunction follow-up glomerular filtration high risk inflammatory marker kidney cell kidney dysfunction kidney epithelial cell molecular phenotype novel novel therapeutic intervention outcome forecast pandemic disease parent grant podocyte prevent prospective rat KIM-1 protein recruit respiratory solute targeted biomarker tool urinary

项目摘要

PROJECT ABSTRACT Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 has been identified within multiple cell types of the kidneys, including tubular epithelial cells, endothelial cells, and podocytes, suggesting pathologic effects. Early clinical data suggest a greater incidence and severity of acute kidney injury (AKI) in persons who have COVID-19; however, existing studies lack comparisons with similarly ill persons who do not have COVID-19, preventing reliable assessment of the causal impact of SARS-CoV-2 on kidney injury and function. Most underlying causes of AKI involve injury to tubular epithelial cells and their microenvironment. Yet, the prevailing clinical assessment of kidney function in AKI is based on incremental changes in serum creatinine concentrations under the assumption that glomerular filtration and tubular functions are tightly coupled within an individual. To challenge this assumption, our parent NIDDK funded grant, “Role of Kidney Proximal Tubular Secretion in Critical Illness” (R01DK124063, PI Kestenbaum) is recruiting a prospective cohort of critically ill adults without COVID-19, quantifying tubular secretory clearance using a novel assay that we have developed, and determining the impact of this intrinsic kidney function on prognosis and kidney drug dosing. In this supplement, we propose to expand the unique tools of the parent grant to delineate the impact of SARS- CoV-2 on the kidney tubules. To accomplish this goal, we will comprehensively characterize kidney tubular functions in the Covid-19 Host Response and Outcomes (CHROME) study, an ongoing prospective study of critically ill persons with COVID-19 that includes a comparison group of similarly ill persons without COVID-19. To our existing measurements of tubular secretory clearance, we will add markers of tubular synthesis, distal tubular viability, and tubular injury. We will test whether COVID-19 is associated with changes in these tubular processes over the course of hospitalization and with persistent kidney dysfunction at 30-day follow-up.

项目摘要 2019 年冠状病毒病（COVID-19）是由严重急性呼吸系统综合症引起的全球大流行冠状病毒-2 (SARS-CoV-2) 已在肾脏的多种细胞类型中被发现，包括肾小管上皮细胞、内皮细胞和足细胞，提示早期临床效应。数据表明，COVID-19 患者急性肾损伤 (AKI) 的发生率和严重程度更高；然而，现有研究缺乏与未感染 COVID-19 的类似疾病患者的比较，因此可靠评估 SARS-CoV-2 对肾损伤和功能的因果影响。 AKI 的大多数根本原因涉及肾小管上皮细胞及其微环境的损伤。 AKI 肾功能的流行临床评估基于血清肌酐的增量变化假设肾小球滤过和肾小管功能紧密耦合的浓度为了挑战这个假设，我们的母公司 NIDDK 资助了一项名为“肾近端管状的作用”的拨款。 “危重病秘书”（R01DK124063，PI Kestenbaum）正在招募一批危重病患者没有 COVID-19 的成年人，使用我们开发的新型测定法量化肾小管分泌清除率，并确定这种内在肾功能对预后和肾脏药物剂量的影响。在本补充文件中，我们建议扩大家长补助金的独特工具，以描述 SARS 的影响肾小管上的 CoV-2 为了实现这一目标，我们将全面表征肾小管。 Covid-19 宿主反应和结果 (CHROME) 研究中的功能，这是一项正在进行的前瞻性研究患有 COVID-19 的危重患者，其中包括未患 COVID-19 的类似疾病患者的对照组。在现有的肾小管分泌清除率测量中，我们将添加肾小管合成、远端的标记物我们将测试 COVID-19 是否与这些肾小管的变化有关。住院期间的过程以及 30 天随访时持续肾功能障碍。