Tuesday, April 16, 2024
4/16/2024
PROJECT SUMMARY Heart failure leads to >1.4 million hospitalizations annually in the U.S. During these acute decompensated heart failure (ADHF) hospitalizations, the kidneys’ health influences almost every aspect of management, including initial diuretic dosing, treatment intensification, and discharge planning. However, clinical reliance on serum creatinine, an insensitive, nonspecific and often misleading kidney biomarker, substantially contributes to suboptimal ADHF treatment. Although guidelines suggest that clinicians use the patient’s kidney function as an indicator for the initial diuretic dose, the creatinine is actually a poor predictor of diuretic response and clinicians must resort to “trial and error” in searching for each patient’s optimal dose. Further, although creatinine elevations during treatment commonly reflect beneficial effects, clinicians typically de-escalate diuresis from fear of worsening kidney damage. During discharge planning, this fear also drives clinicians to prescribe an oral diuretic dose that is too low, and to avoid beneficial therapies. These obstacles to ideal care culminate in delayed symptom relief, prolonged hospitalization, frequent readmissions, and high mortality risk. Given the kidney tubules’ central role in determining the effectiveness and safety of ADHF pharmacological treatment, clinicians need tools that capture kidney tubule health to optimize diuretic strategies, improve delivery of guideline-directed medical therapy, and minimize the risk for true kidney damage. In ambulatory settings, our team has demonstrated the remarkable ability of tubule health measures to detect kidney damage early, to reflect the kidneys’ response to treatment more accurately that creatinine, and to predict long-term outcomes. Early studies of a few tubule markers in ADHF show that they improve in proportion to diuretic response and have tremendous potential to change how kidney health is monitored during ADHF treatment. Given the central role of kidney health in ADHF treatment and prognosis, our overall goals are to fundamentally change how clinicians approach kidney health monitoring and clinical decision-making during ADHF treatment. To achieve these goals, we will capitalize on the well-characterized Mechanisms of Diuretic Resistance (MDR) Study, a cohort of patients hospitalized for ADHF who have undergone serial biospecimen collections timed to diuretic treatment throughout hospitalization with longitudinal follow-up for key clinical outcomes. We will measure a broad panel of kidney biomarkers that reflect tubule reabsorptive and secretory functions, injury, synthetic and reparative capacity, and tubulointerstitial inflammation and fibrosis. We will identify which tubule health measures most effectively: 1) predict treatment response to initial loop diuretic dosing and adjunctive diuretic therapy (Aim 1); 2) discern pseudo- from intrinsic kidney damage among patients with creatinine elevations during treatment (Aim 2); and 3) identify patients appropriate for discharge and distinguish their risks for subsequent adverse events (Aim 3). This project will lay the necessary groundwork for a clinical trial to test a kidney biomarker-guided ADHF treatment strategy.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
