The incidence of AKI is 20-30% in patients hospitalized with COVID-19 in the United States, and is over 40% in patients admitted to the ICU. Moreover, the mortality rate in patients that experience AKI in the setting of COVID-19 is approximately 2- to 10-fold higher than patients without AKI. The pathogenesis of AKI in COVID-19 infection remains unclear and it is not known if the injury to the tubule is direct result of the virus infection or if it is secondary to other organ complications. Availability of urine, blood and tissue samples early in the course of infection will provide important pathogenic insights for therapeutic and clinical management. The Translational Research investigating Biomarker Endpoints (TRIBE)-AKI consortium has a long-standing history of conducting multidisciplinary epidemiologic and translational research studies in the setting of AKI. They have experience with long term follow-up of hospitalized patients, tissue and sample handling as well as analytic considerations. We propose a prospective observational study of the clinical and biologic predictors of major adverse kidney events and death (MAKE-D) in COVID-19, including the following: severity of AKI (stages 1, 2, 3 and requiring dialysis), mortality, and non-recovery of AKI and transition to chronic kidney disease. We will examine consecutive patients hospitalized with COVID-19 at three premier academic hospitals participating in the TRIBE consortium: Johns Hopkins Medicine, Mount Sinai Hospital and Yale-New Haven Hospital. We assess the incidence, severity, and clinical predictors of MAKE-D during hospitalization and at 90 days following discharge. We will investigate the possible role of injury, inflammation and repair mechanisms through biomarkers in the blood and urine in serial samples collected from patients during hospitalization. We will also perform advanced evaluation of kidney biopsies using single cell RNA sequencing to identify possible mechanistic disease pathways, which may lead to novel therapeutic targets. Combating this pandemic will require a multidisciplinary approach from the medical research community, including rigorously conducted epidemiologic studies that include granular patient- level data and translational research studies to understand the pathogenesis of COVID- associated kidney disease.

Public Health Relevance

Over a third of patients hospitalized with COVID-19 suffer from acute kidney injury and its complications. Using data and samples from three premier academic centers, the project will identify the risk factors and mechanisms for patients who will develop these complications. The project has potential to provide important pathogenic insights for therapeutic and clinical management of COVID-19.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK093770-09S1
Application #
10177020
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Abbott, Kevin C
Project Start
2012-08-15
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
9
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Hall, Isaac E; Parikh, Chirag R; Schröppel, Bernd et al. (2018) Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival. Transplant Direct 4:e373
Mansour, Sherry G; Hall, Isaac E; Reese, Peter P et al. (2018) Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing. Clin Transplant 32:e13441
Hall, Isaac E; Akalin, Enver; Bromberg, Jonathan S et al. (2018) Deceased-donor acute kidney injury is not associated with kidney allograft failure. Kidney Int :
Moledina, Dennis G; Parikh, Chirag R (2018) Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin Nephrol 38:3-11
Harhay, Meera Nair; Jia, Yaqi; Thiessen-Philbrook, Heather et al. (2018) The association of discharge decisions after deceased donor kidney transplantation with the risk of early readmission: Results from the deceased donor study. Clin Transplant 32:e13215
Mansour, S G; Puthumana, J; Reese, P P et al. (2017) Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes. Kidney Int Rep 2:749-758
Moledina, Dennis G; Hall, Isaac E; Thiessen-Philbrook, Heather et al. (2017) Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury. Am J Kidney Dis 70:807-816
Hall, Isaac E; Reese, Peter P; Doshi, Mona D et al. (2017) Delayed Graft Function Phenotypes and 12-Month Kidney Transplant Outcomes. Transplantation 101:1913-1923
Doshi, Mona D; Reese, Peter P; Hall, Isaac E et al. (2017) Utility of Applying Quality Assessment Tools for Kidneys With KDPI ?80. Transplantation 101:1125-1133
Puthumana, Jeremy; Hall, Isaac E; Reese, Peter P et al. (2017) YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation. J Am Soc Nephrol 28:661-670

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