Towards improving recovery from dialysis-requiring acute kidney injury

改善需要透析的急性肾损伤的恢复

• 批准号: 10600072
• 负责人: Ian McCoy
• 金额: $ 19.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600072
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Biological Markers; Biometry; Board Certification; Clinical; Clinical Research; Collection; Complication; Creatinine clearance measurement; Data Collection; Databases; Diagnosis; Dialysis procedure; Discrimination; Diuretics; Dose; Dropout; Electrolytes; End stage renal failure; Epidemiology; Event; Family; Fostering; Funding; Goals; Guidelines; Health Care Costs; Hemodialysis; Hospitalization; Hospitals; Hour; Hypotension; Injury; Injury to Kidney; Intervention; Intervention Trial; Investigation; K-Series Research Career Programs; Kidney; LCN2 gene; Learning; Life; Life Expectancy; Literature; Manuscripts; Master of Science; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Monitor; Multicenter Trials; Observational Study; Occupations; Outpatients; Patient-Focused Outcomes; Patients; Peer Review; Pilot Projects; Publishing; Quality of life; Randomized; Randomized, Controlled Trials; Recovery; Recurrence; Renal Replacement Therapy; Renal function; Research; Research Infrastructure; Research Personnel; Risk; Safety; Schedule; Sodium; Spottings; Sum; Temperature; Time; Time trend; Training; Urine; Withdrawal; Work; arm; biobank; career; clinical practice; design; experience; falls; hemodynamics; improved; injury and repair; innovation; mortality; multi-component intervention; novel; participant enrollment; patient oriented research; pilot trial; prevent; renal ischemia; repaired; safety outcomes; skills; timeline; trial enrollment; urinary

PROJECT SUMMARY / ABSTRACT Dialysis-requiring acute kidney injury (AKI-D) is a profoundly life-altering event for which there are currently no treatments to improve the chances of renal recovery. Moreover, there are no clinical guidelines to help clinicians determine when to discontinue dialysis in AKI-D as the kidneys recover. Earlier and more frequent dialysis discontinuation would have powerful impacts on patient quality of life, life expectancy, and healthcare costs. The overarching theme of this proposal is to investigate ways to foster earlier and more frequent recovery from AKI-D, allowing independence from acute dialysis. The three specific aims are: Aim 1: To quantify the association between measured creatinine clearance (CrCl) from timed urine collections and the risk of requiring another dialysis treatment in the next week among hospitalized patients with AKI-D. Aim 2: To evaluate the associations among urinary biomarkers of injury and repair and renal recovery among hospitalized patients with AKI-D. Aim 3: To pilot a separate outpatient trial evaluating the feasibility, tolerability, and safety of a multicomponent intervention (cooled dialysate, high sodium dialysate, high dose diuretics) designed to prevent intradialytic hypotension during the course of established AKI-D. This K23 proposal will give Ian McCoy, MD, MS the protected time, mentorship, training, and research experience needed to become independent in patient-oriented research. Dr. McCoy is a board-certified nephrologist and clinical researcher, establishing himself as a young investigator in AKI. He has published several first-authored, peer-reviewed manuscripts on AKI, completed a Master’s degree in Epidemiology, and turned down other job offers to pursue a career in clinical AKI research. Dr. McCoy came to UCSF to take advantage of the research infrastructure of an ongoing randomized controlled trial enrolling AKI-D patients in the hospital established by his mentors Drs. Chi-yuan Hsu and Kathleen Liu (The Liberation from Acute Dialysis [LIBERATE-D]) study. Drs. Hsu and Liu together with Dr. John Neuhaus make a world-class mentoring team with relevant expertise in clinical research in AKI and biostatistics. All three aims are innovative and importantly feasible within a K23 timeline and scope of work. Somewhat unusual for a career development award, the aims in this proposal have the potential to directly change clinical practice. For instance, measured CrCl from timed urine collections are commonly used in routine clinical practice (Aim 1), and several of the biomarkers being evaluated (NGAL, TIMP-2*IGFBP7) are commercially available (Aim 2). The pilot trial proposed in Aim 3 may eventually lead to a practice-changing multicenter trial if successful. In the next five years, Dr. McCoy will gain experience in primary data collection and interventional trials, and obtain independent research funding (R01 or equivalent) for further investigations in AKI.

项目总结/摘要 需要透析的急性肾损伤（AKI-D）是一种严重改变生命的事件，目前尚无 治疗，以提高肾脏恢复的机会。此外，没有临床指南可以帮助 临床医生决定当肾脏恢复时，AKI-D患者何时停止透析。更早更频繁 透析中止将对患者的生活质量、预期寿命和医疗保健产生重大影响 成本该提案的首要主题是研究如何更早、更频繁地促进 从AKI-D中恢复，允许独立于急性透析。这三个具体目标是： 目的1：定量测定定时尿液采集的肌酐清除率（CrCl） 以及AKI-D住院患者在下周需要再次透析治疗的风险。 目的2：评价尿损伤和修复生物标志物与肾功能恢复之间的关系， AKI-D住院患者。 目的3：开展一项单独的门诊试验，评估多组分药物的可行性、耐受性和安全性。 干预（冷却透析液、高钠透析液、高剂量利尿剂），旨在预防透析中 在确定的AKI-D过程中发生低血压。 这个K23提案将给伊恩麦考伊，医学博士，MS的保护时间，导师，培训和研究 在以病人为导向的研究中，需要有独立的经验。麦考伊博士是一位 肾脏病学家和临床研究者，确立了自己作为阿基年轻研究者的地位。他已经出版 几篇关于阿基的第一作者、同行评审的手稿，完成了流行病学硕士学位， 她拒绝了其他工作机会，转而从事临床阿基研究。麦考伊医生来到加州大学旧金山分校 一项正在进行的招募AKI-D患者的随机对照试验的研究基础设施的优势， 他的导师许致远和刘琳博士创办的医院（从急性解放 透析[LIBERATE-D]）研究。徐博士和刘博士与John Neuhaus博士一起进行世界级的指导 拥有阿基临床研究和生物统计学相关专业知识的团队。这三个目标都是创新的， 在K23时间轴和工作范围内是非常可行的。对于一个职业发展来说 获奖后，该提案中的目标有可能直接改变临床实践。例如，测量 来自定时尿液采集的CrCl通常用于常规临床实践（目的1）， 正在评估的生物标志物（NGAL、TIMP-2* IGFBP 7）是市售的（Aim 2）。试点试验 如果成功的话，目标3中提出的方法最终可能会导致实践改变的多中心试验。未来五 麦考伊博士将获得主要数据收集和干预性试验的经验，并获得 独立研究基金（R 01或同等项目），用于阿基的进一步研究。