Towards improving recovery from dialysis-requiring acute kidney injury

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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.