The Assessment of Acute Kidney Injury Sub-phenotypes in the Intensive Care Unit

重症监护室急性肾损伤亚表型的评估

• 批准号: 10543081
• 负责人: Pavan Kumar Bhatraju
• 金额: $ 18.57万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543081
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Affect; Award; Biological; Biological Markers; Biology; Biometry; Blood Vessels; Cell Cycle Arrest; Cessation of life; Characteristics; Classification; Clinical; Clinical Data; Complement; Creatinine; Critical Care; Critical Illness; DNA; Data; Development; Dialysis procedure; Discipline; Education; Endothelium; Enrollment; Epidemiologist; Epidemiology; Evaluation; Event; Foundations; Functional disorder; Funding; Genes; Genetic; Genetic Risk; Genetic Variation; Goals; Heterogeneity; Hospitals; Individual; Inflammation; Injury; Injury to Kidney; Intensive Care Units; Interdisciplinary Study; K-Series Research Career Programs; Kidney; Lung; Manuscripts; Medicine; Mentorship; MicroRNAs; Modeling; Molecular; Molecular Epidemiology; Morbidity - disease rate; Nephrology; Outcome; Pathway interactions; Patient Admission; Patients; Pattern; Pharmacotherapy; Phenotype; Physicians; Plasma; Population; Post-Transcriptional Regulation; Process; Prospective Studies; Protein Analysis; Public Health; Public Health Schools; Renal function; Research; Research Infrastructure; Research Institute; Research Methodology; Research Proposals; Research Support; Research Training; Risk; Risk Estimate; Risk Factors; SP1 gene; Sampling; Science; Scientist; Serum; Syndrome; Techniques; Testing; Training; Training Programs; Translational Research; Tubular formation; Universities; Urine; Validation; Variant; Washington; Work; biological heterogeneity; career; clinical heterogeneity; cohort; drug development; endothelial dysfunction; genetic risk factor; genome sciences; genome-wide analysis; hazard; improved; innovation; mortality; novel; pharmacologic; precision medicine; predictive modeling; prevent; prognostication; prospective; secondary analysis; skills; therapeutic target; translational applications; translational scientist; urinary

Project Summary/Abstract Pavan Bhatraju, MD, MSc plans for a career as a molecular epidemiologist physician scientist in the field of acute kidney injury (AKI) in the intensive care unit (ICU). The objective of the proposed career development award is to provide necessary training in research methods to facilitate Dr. Bhatraju’s transition to independent research. The mentorship available at the University of Washington (UW) in the Division of Pulmonary and Critical Care Medicine (PCCM) and the Kidney Research Institute are outstanding. He will continue his work under the mentorship of Drs. Mark Wurfel (PCCM) and Jonathan Himmelfarb (Nephrology) at the UW. Collaborators on his multi-disciplinary research team span the disciplines of genome sciences (Dr. Gail Jarvik), epidemiology and biostatistics (Dr. Ronit Katz) and the application of translational research to the study of AKI (Dr. Chirag Parik). To complement the support from this research team, Dr. Bhatraju will augment his Masters in Science in Epidemiology with advanced coursework at the nationally-renowned UW School of Public Health. AKI is common in the ICU and is associated with morbidity and mortality. Currently we have no effective pharmacological therapy for AKI. Limitations in drug development may be partly explained by the biological and clinical heterogeneity in patients included in the AKI phenotype. To address these limitations, our lab has identified two distinct AKI sub-phenotypes (also known as endotypes) using an innovative modeling approach, latent class analysis. We found that the two AKI sub-phenotypes had different clinical characteristics, biomarker patterns and risk of poor short-term outcomes. We also developed and validated a 3-variable prediction model to prospectively identify the AKI sub-phenotypes. Overall, these findings provide the foundation for Dr. Bhatraju’s K23 research proposal. The objectives of the proposed research include: 1) evaluate the association of AKI sub-phenotypes with major adverse kidney events by 1 year; 2) determine the genetic risk factors associated with the development of AKI sub-phenotypes, and; 3) identify specific pathophysiologic differences between the AKI sub-phenotypes through a targeted urinary protein analysis. This award will provide essential research training in genome sciences, biostatistics, advanced epidemiology and will broaden his bench lab skillset. This proposal leverages Dr. Bhatraju’s unique access to multiple critically ill cohorts, access to a research infrastructure at the UW to enroll a prospective ICU cohort collecting urine, plasma and DNA samples and access to world-class didactic training program at the UW School of Public Health. His overall research goal is to use techniques of molecular epidemiology to develop a pathophysiologic based classification of patients with AKI to improve risk prognostication, discover novel genetic risk factors and inform precision based strategies to prevent and treat the development of AKI in the ICU. With the support of this K23, the research and education agenda Dr. Bhatraju has devised will assist him in achieving his long-term goal of becoming an independent translational investigator conducting AKI research.

项目总结/文摘

项目成果

Sub-Phenotypes of Acute Kidney Injury: Do We Have Progress for Personalizing Care?

• DOI: 10.1159/000511321
• 发表时间: 2020
• 期刊: Nephron
• 影响因子: 2.5
• 作者: Thau MR;Bhatraju PK
• 通讯作者: Bhatraju PK

Emergency department characteristics and associations with intensive care admission among patients with coronavirus disease 2019.

• DOI: 10.1002/emp2.12350
• 发表时间: 2021-03
• 期刊: Journal of the American College of Emergency Physicians open
• 影响因子: 2.3
• 作者: Krieger J;McGuire F;Risa E;Longino A;Coppess S;Riveros T;Hebert C;Town J;Bhatraju P;Johnson N
• 通讯作者: Johnson N

Subphenotypes in acute kidney injury: a narrative review.

• DOI: 10.1186/s13054-022-04121-x
• 发表时间: 2022-08-19
• 期刊: Critical care (London, England)

Is There One Best Way to Define AKI?

有没有一种最佳方法来定义 AKI？

• DOI: 10.34067/kid.0002972022
• 发表时间: 2022
• 期刊: Kidney360
• 作者: Zelnick,LeilaR;Bhatraju,PavanK
• 通讯作者: Bhatraju,PavanK

A Description of Mechanically Ventilated Patients Admitted From the Emergency Department With a Short Critical Care Stay.

急诊科入院接受短期重症监护的机械通气患者的描述。

• DOI: 10.1016/j.jemermed.2023.02.024
• 发表时间: 2023
• 期刊: The Journal of emergency medicine
• 作者: Krieger,JoshuaA;Hernandez,MichaelA;Sheehan,JordanC;Mitchell,StevenH;Carlbom,DavidJ;Robinson,EllenF;Town,JamesA;Bann,MaralyssaA;Thau,MatthewR;Bhatraju,PavanK;Robinson,BryceRH;Johnson,NicholasJ
• 通讯作者: Johnson,NicholasJ