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Principal Investigator: BRYAN R KESTENBAUM
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2020
Award: $500,000
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
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.
Terms: <2019 novel coronavirus><2019-nCoV><21+ years old><ARDS><Active Follow-up><Acute><Acute Renal Failure with Renal Papillary Necrosis><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Address><Adult><Adult ARDS><Adult Human><Adult RDS><Adult Respiratory Distress Syndrome><Amino Acids><Aminopeptidase><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Angiotensin Receptor><Angiotensins><Anthelone U><Arginine><Assay><Autopsy><Binding Proteins><Bioassay><Biologic Assays><Biological><Biological Assay><Blood Plasma><Blood Serum><CD143 Antigens><COVID-19><COVID19><Carboxycathepsin><Case Series><Catalogs><Cell Body><Cell surface><Cells><Cessation of life><Citrulline><Clinical><Clinical Data><Clinical assessments><Coupled><Creatinine><Critical Illness><Critically Ill><Da Nang Lung><Death><Dipeptidyl Peptidase A><Disease><Disorder><Distal><Dose><Drug Synthesis and Chemistry><Drugs><Dysfunction><Endocrine Gland Secretion><Endothelial Cells><Enrollment><Epidermal Growth Factor><Epidermal Growth Factor-Urogastrone><Epithelial Cells><Failure><Filtration><Filtration Fractionation><Functional disorder><Funding><Goals><Grant><Hormones><Hospital Admission><Hospitalization><Hypoxemia><Immune response><Immunological response><Impairment><Incidence><Individual><Inflammatory><Injury><Injury to Kidney><Kidney><Kidney Tubules><Kidney Urinary System><Kininase A><Kininase II><Knowledge><L-Arginine><LCN2><LCN2 gene><Ligand Binding Protein><Ligand Binding Protein Gene><Lipocalin 2><Measurement><Measures><Mediating><Medication><NGAL><NIDDK><National Institute of Diabetes and Digestive and Kidney Diseases><Neutrophil Gelatinase-Associated Lipocalin><Oncogenic Lipocalin 24P3><Outcome><Parents><Pathogenesis><Pathologic><Pathway interactions><Patients><Pattern><Peptidyl-Dipeptidase A><Persons><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Physiologic><Physiological><Physiopathology><Plasma><Plasma Serum><Process><Prognosis><Prospective Studies><Prospective cohort><Prospective cohort study><Protein Binding><Protein Secretion><Renal Cell><Renal function><Renal tubule structure><Reporting><Reticuloendothelial System, Serum, Plasma><Role><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Serum><Severe acute respiratory syndrome coronavirus 2><Severities><Severity of illness><Shock Lung><Stiff lung><System><Testing><Therapeutic Hormone><Thrombosis><Time><Tubular><Tubular formation><Urogastrone><Uterocalin><Viral><Visceral Epithelial Cell><Wuhan coronavirus><active followup><acute kidney injury><adulthood><aminoacid><base><beta-Urogastrone><biomarker development><bound protein><cell type><clinical significance><clinically significant><cohort><comparator group><comparison group><corona virus disease 2019><coronavirus disease 2019><disease severity><drug synthesis><drug/agent><endothelial dysfunction><enroll><follow up><follow-up><followed up><followup><glomerular filtration><glomerular visceral epithelial cell><high risk><host response><hypoxemic><immunoresponse><inflammation marker><inflammatory marker><injuries><kidney cell><kidney dysfunction><kidney epithelial cell><kidney function><kidney injury><kidney injury molecule 1><molecular phenotype><necropsy><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><novel><novel therapeutic approach><novel therapeutic intervention><novel therapy approach><outcome forecast><pandemic><pandemic disease><parent grant><pathophysiology><pathway><podocyte><postmortem><prevent><preventing><prospective><rat KIM-1 protein><recruit><renal><renal KIM-1><renal dysfunction><renal injury><renal tubule><respiratory><social role><solute><targeted biomarker><thrombotic disease><thrombotic disorder><tool><urinary><wet lung>