Cardiac Output and Renal Perfusion Alterations in the Development of Acute Kidney Injury in Cardiac Surgery - PROJECT SUMMARY Dr. Lee Goeddel is a cardiac anesthesiologist and intensivist at Johns Hopkins University (JHU) with the long- term goal of becoming a leader in perioperative organ protection. He is developing expertise in data science methodologies, urine biomarkers of renal tubular injury, and ultrasound imaging of renal blood flow to better understand the role of hypoperfusion-related acute kidney injury (AKI) during cardiac surgery. Up to 39% of cardiac surgery patients experience AKI which drastically increases their risk of death or chronic kidney disease. Though animal and human studies have demonstrated that low cardiac output (CO) can impair renal perfusion and cause AKI, the relationship between CO, renal perfusion, and AKI in cardiac surgery is unclear. His long- term research goal is to determine the optimal approach to monitor and treat CO and renal perfusion to prevent AKI. This proposal addresses this gap and will provide the structured mentorship and necessary expertise to achieve his goals. He has assembled an exceptional team of committed mentors at JHU. Co-primary mentor nephrologist Chirag Parikh, MD, PhD, is a leader in AKI research and founder of the TRIBE-AKI consortium. Co- primary mentor, biostatistician Karen Bandeen-Roche, PhD, has broad expertise in the mechanistic analysis and modeling of complex diseases. Co-mentor Ciprian Crainiceanu, PhD, pioneered analytic tools to assess high dimensional time series data to address public health problems. Co- mentor Charles Brown MD, MHS is a cardiac anesthesiologist and PI of an NIH-funded cohort study examining cerebrovascular perfusion in cardiac surgery. Cardiology co-mentor, Joao Lima, MD, has served as PI in several multicenter studies using novel imaging methods. Dr. Goeddel will learn critical skills in clinical investigation, biostatistics, and AKI pathophysiology and complete a PhD synchronized to the learning plan. This will uniquely position him to dissect the mechanisms of AKI in the controlled environment of the operating room. The exceptional environment at JHU is ideal for Dr. Goeddel’s growth. His research will clarify the association between low CO and AKI in a large cardiac surgery cohort (data science- Aim 1) addressing the role of all key factors (like vasopressors). Dr. Goeddel will calculate continuous CO (every 5 seconds) from arterial blood pressure (120 Hz) in a stored cohort using an FDA algorithm that is clinically available and validated to the gold standard measurement of CO. In Aim 2, he will enroll the HARBOR-AKI (Hemodynamics and Renal Biomarkers to clarify OR associated AKI) prospective cohort to assess the association between low CO and urinary biomarkers of renal tubular injury that rise sooner after injury with more sensitivity for ischemic AKI than serum creatinine to clarify the timing and physiology of CO related ischemic AKI. In Aim 3, Dr. Goeddel will use standard ultrasound imaging during surgery to repeatedly measure renal vein blood flow (3a) to relate renal perfusion to urine injury markers, and (3b) to explore the determinants of adequate renal perfusion (independent and dependent of CO). The skills and knowledge Dr. Goeddel develops will enable his goal to become an independent investigator prepared to lead key studies to prevent AKI in cardiac surgery.
