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.

项目概要/摘要 需要透析的急性肾损伤（AKI-D）是一种深刻改变生活的事件，目前尚无治疗方法 此外，没有临床指南可以提供帮助。 随着肾脏恢复的更早和更频繁，羊群决定何时停止 AKI-D 透析。 停止透析将对患者的生活质量、预期寿命和医疗保健产生重大影响 该提案的首要主题是研究如何更早、更频繁地进行培养。 从 AKI-D 中恢复，摆脱急性透析的三个具体目标是： 目标 1：量化定时尿液采集测量的肌酐清除率 (CrCl) 之间的关联 以及 AKI-D 住院患者下周需要再次透析治疗的风险。 目标 2：评估损伤和修复的尿液生物标志物与肾脏恢复之间的关联 患有 AKI-D 的住院患者。 目标 3：进行一项单独的门诊试验，评估多组分的可行性、耐受性和安全性 干预措施（冷却透析液、高钠透析液、高剂量利尿剂）旨在预防透析中 已确定的 AKI-D 过程中的低血压。 该 K23 提案将为医学博士、理学硕士 Ian McCoy 提供受保护的时间、指导、培训和研究 麦考伊博士是经过委员会认证的独立从事以患者为中心的研究所需的经验。 肾脏病学家和临床研究员，将自己定位为 AKI 领域的年轻研究者。 撰写了几篇关于 AKI 的第一作者、同行评审的手稿，完成了流行病学硕士学位，并且 McCoy 博士拒绝了其他工作机会，转而从事 AKI 临床研究。 一项正在进行的随机对照试验的研究基础设施的优势，该试验招募了 AKI-D 患者 由他的导师许志远医生和凯瑟琳刘医生建立的医院（从急性中解放出来） 透析 [LIBERATE-D]）Hsu 博士和 Liu 与 John Neuhaus 博士一起进行了世界级的指导。 拥有 AKI 和生物统计学临床研究相关专业知识的团队这三个目标都是创新和的。 重要的是在 K23 时间表和工作范围内可行 对于职业发展来说有些不寻常。 获奖，该提案的目标有可能直接改变临床实践。 定时尿液采集中的 CrCl 通常用于常规临床实践（目标 1），并且其中一些 正在评估的生物标志物（NGAL、TIMP-2*IGFBP7）已上市（目标 2）。 如果成功的话，目标 3 中提出的目标最终可能会导致改变实践的多中心试验。 年，McCoy 博士将获得主要数据收集和介入试验的经验，并获得 用于进一步研究 AKI 的独立研究资金（R01 或同等资金）。