Relation between acute changes in kidney function with clinical outcomes among patients with heart failure - ABSTRACT Baseline reduced kidney function is highly prevalent among patients with acute heart failure (AHF) and is one of the most powerful risk factors for adverse clinical outcomes. The association between acute kidney function declines and outcomes, however, remain controversial, with some studies showing acute declines in estimated glomerular filtration (eGFR) to be associated with worse outcomes but other studies not. The goal of Dr. McCallum’s proposal is to better understand the mechanisms of acute eGFR declines that occur in the setting of AHF and examine how acute eGFR declines are related to outcomes including long term kidney function, mortality and AHF hospitalizations. The overall hypothesis is that three key components—congestion, cardiac hemodynamics, and neurohormonal (NH) activity—are the primary risk factors for acute eGFR declines, and that the relation between acute eGFR declines and clinical outcomes needs to be interpreted within the context of changes in these three factors. In order to examine these relations, her Aims would include 1) retrospective analysis of patients admitted to Tufts Medical Center for AHF and requiring a pulmonary artery (PA) catheter (n=890) for repeated measures of congestion and cardiac hemodynamics; 2) prospective enrollment of 140 patients admitted to Tufts Medical Center for AHF with an indwelling PA catheter to assay for repeated measures of plasma NH activity; and 3) adoption of multi-trajectory modeling to develop clinical phenotypes of acute cardiorenal syndrome (CRS) by incorporating trajectories of eGFR change, congestion, cardiac hemodynamics, and NH activity. The career development plan incorporates didactic training in longitudinal data analysis including joint modeling and multi-trajectory modeling, biomarker methodology, introductory informatics for electronic health record research, as well as immersion and practical training in cardiac hemodynamics and prospective patient recruitment, all under the mentorship of an experienced group of nephrologists, cardiologists and statisticians with expertise in various aspects of the CRS. Successful completion of these aims is feasible, as shown by Dr. McCallum’s preliminary data under her institutional KL2 funding, as well her track record of productivity under her primary mentor Dr. Mark Sarnak. Her co-mentor will be Dr. Jeffrey Testani, a cardiologist and Director of Heart Failure Research at Yale University who has expertise in the CRS, has collaborated with Dr. McCallum on several manuscripts, and has incorporated her into his research group and sponsored several trips for her to his research lab at Yale. With this K23 award, Dr. McCallum will receive extensive training in biostatistical methods, dataset creation, CRS pathophysiology, biomarker methodology, primary data collection and prospective study design. In aggregate, completion of these aims will provide Dr. McCallum with expertise in the CRS and arm her with the tools necessary to successfully compete for independent funding.
