Utilizing Biosignals and Biomarkers to Improve the Safety and Efficacy of Albumin Infusion in Patients with Cirrhosis and Acute Kidney Injury

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

Abstract Cirrhosis is the end result of all chronic liver diseases and is a leading cause of death. One of the deadliest complications of cirrhosis is acute kidney injury (AKI). AKI in patients with cirrhosis has three main causes that comprise 99% of cases however they are often indistinguishable at presentation: volume depletion, hepatorenal syndrome (HRS-AKI), and Acute Tubular Necrosis (ATN). The first diagnostic and therapeutic intervention for AKI is albumin infusion in an attempt to boost kidney perfusion by increasing intravascular volume. However, this can cause life threatening volume overload in patients who do not have volume depletion and increases mortality in patients with HRS-AKI due to delaying initiation of vasoconstrictors. Novel methods to determine intravascular volume status and to distinguish causes of AKI are desperately needed. This proposal seeks to fill this critical knowledge gap. The central hypothesis of this project is that biomarker and pulse oximeter waveform (photoplethysmography, PPG) can augment clinical data to predict AKI response to albumin infusion in patients with cirrhosis. The aims are 1) Predict the benefits (1A) and harms (1B) of albumin infusion for AKI among a retrospective cohort using clinical data, 2) Define a PPG ‘biosignature’ associated with circulatory volume changes after albumin infusion in patients with cirrhosis and 3) Create a model using clinical data augmented by biosignals to predict albumin benefit in a prospective cohort of patients with cirrhosis (3A) and explore the utility of adding urinary biomarkers (3B). Dr. Mazumder’s preliminary work shows that the contour of a simple pulse oximeter waveform (PPG) can predict intravascular volume status. Urinary biomarkers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) have preliminary evidence suggesting a role in distinguishing between ATN and other causes of AKI among patients with cirrhosis. Dr. Mazumder will apply these preliminary findings to improve the safety and efficacy of albumin infusion in reversing AKI in patients with cirrhosis. These proposed studies will enhance our understanding of the landscape of AKI in cirrhosis and how bedside, physiologic biosignals and biomarkers can personalize care for patients. During this K23 award, Dr. Mazumder will also achieve four training aims: 1) Repeated Measures and Missing Data, 2) Signals Analysis and Machine Learning, 3) Running a prospective clinical study with biomarker exploration, and 4) Grant writing for independent funding. He will achieve these aims with the support of an experienced mentor team that includes Drs. Elliot Tapper (training aims 1, 3, and 4), Anna Lok (training aims 3 and 4), Dr. Laura Mariani (training aims 3 and 4) and Dr. Kayvan Najarian (training aims 1 and 2). Dr. Mazumder will benefit from a supportive institutional environment, formal classwork, and by attending academic meetings in the field. Fulfilling this award’s research and training aims will propel Dr. Mazumder into an independent investigator in portal hypertension.