Application of Novel Biomarkers of Renal Health in Cirrhosis Patients to Stratify Risk of Acute Kidney Injury Occurrence and Reversibility

PROJECT SUMMARY/ABSTRACT Cirrhosis is a leading cause of morbidity and mortality among adults in the United States. Acute kidney injury (AKI) is a common, expensive, and lethal complication of cirrhosis. The strongest predictor of AKI in cirrhosis patients, regardless of etiology, is chronic kidney disease (CKD), as measured by estimated glomerular filtration rate (eGFR). Given that there is a rising incidence of both AKI and CKD in this population, there is a developing critical need for clinical tools that identify cirrhosis patients at risk for AKI before its development. This proposal’s three research aims address this need. Leveraging an ongoing cohort with >1000 decompensated cirrhosis patients with >2500 banked biospecimens, these aims will: (1) establish the independent association between renal health biomarkers and AKI and compare the discrimination of novel renal health biomarkers to serum creatinine (sCr) to predict AKI (Aim 1); develop and internally validate a clinical risk tool to identify cirrhosis patients most vulnerable to AKI (Aim 2); explore the association between longitudinal changes in renal health biomarkers on AKI reversibility (Aim 3). I am a hepatologist specializing in liver transplantation at the University of California, San Francisco. Through a pilot award provided by the American Association for the Study of Liver Disease, we have generated the preliminary data needed for this application. These data, coupled with a strong foundation of hepatology and nephrology research (Master of Advanced Studies in Clinical Research, >10 publications), have prepared me for this proposal. However, there are several gaps in my training that this NIDDK K23 Career Development Award will address (e.g., cohort development, advanced statistical techniques). Under the direct supervision of a multidisciplinary team of leaders in nephrology (Hsu, Liu), hepatology (Lai), and biostatistics (McCulloch), I will execute a detailed career development plan to accelerate my path toward 4 career goals outlined in this proposal: (1) to develop a foundation of core nephrological principles; (2) to acquire analytic skills to validate biomarker use; (3) to learn novel methodologies at risk prediction, including machine learning techniques; (4) to expand a cohort and to apply methods of longitudinal data analysis. As part of my 5-year plan, I will actively engage in coursework and structured tutorials in nephrology and biostatistics, and interdisciplinary development and leadership programs. In addition, I will integrate myself into the nephrology research community and establish a network of nephrology researchers for current and future collaboration. RELEVANCE: Identifying a metric that captures which cirrhosis patients are at greatest risk for and least likely to reverse from AKI has important clinical implications—it will allow for the implementation of interventions that prevent the occurrence and halt the progression of a major driver of mortality in this population.