Towards improving recovery from dialysis-requiring acute kidney injury

项目摘要/摘要 需要透析的急性肾损伤(AKI-D)是一个深刻改变生活的事件，目前还没有 治疗以提高肾脏恢复的机会。此外，没有临床指南来帮助 随着肾脏的恢复，临床医生决定何时停止AKI-D的透析。更早、更频繁 停止透析将对患者的生活质量、预期寿命和医疗保健产生强大的影响 成本。这项建议的主要主题是调查如何更早和更频繁地促进 从AKI-D恢复，允许独立于急性透析。这三个具体目标是： 目的1：量化定时采集尿液中测得的肌酐清除量(CrCl)之间的关系 以及AKI-D住院患者下周需要再次透析治疗的风险。 目的2：探讨尿液中损伤修复标志物与肾功能恢复的关系。 住院的AKI-D患者。 目标3：试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、大剂量利尿剂)旨在预防透析液中 AKI-D建立过程中的低血压 这项K23计划将为Ian McCoy医学博士和硕士提供受保护的时间、指导、培训和研究 在以病人为中心的研究中需要独立的经验。麦考伊博士是一名经过董事会认证的 肾病学家和临床研究员，在AKI确立了自己作为年轻研究员的地位。他已经出版了 几篇关于AKI的第一次创作和同行评议的手稿，完成了流行病学硕士学位，以及 她拒绝了其他工作机会，转而从事临床AKI研究。麦考伊医生来到加州大学旧金山分校 正在进行的纳入AKI-D患者的随机对照试验的研究基础设施的优势 由他的导师徐志远博士和刘嘉玲博士创办的医院(从急性解放 透析[解放-D])研究。徐博士和刘博士与约翰·纽豪斯博士共同组成世界级的导师 在AKI和生物统计学方面拥有相关临床研究专业知识的团队。这三个目标都是创新的， 重要的是，在K23的时间表和工作范围内是可行的。对于职业发展来说，这有点不寻常 获奖后，这项提案中的目标有可能直接改变临床实践。例如，测量到的 来自定时尿液收集的CRCL通常用于常规临床实践(目标1)，以及几个 正在评估的生物标记物(NGAL、TIMP-2*IGFBP7)已商业化(目标2)。试行 如果成功，AIM 3中提出的建议可能最终导致一项改变做法的多中心试验。在接下来的五年里 几年后，McCoy博士将获得初步数据收集和干预试验的经验，并获得 独立研究经费(R01或等值)，用于AKI的进一步研究。

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.