Individuals receiving maintenance hemodialysis (HD) have exceedingly high mortality, driven largely by cardiovascular causes. Volume-related factors including volume overload, large interdialytic weight gains (IDWGs), and higher ultrafiltration (UF) rates are critical, modifiable contributors to cardiovascular complications such as hypertension, arterial stiffness, left ventricular hypertrophy, and heart failure. Reversing volume overload has been shown to improve blood pressure and cardiac remodeling. Lower IDWGs and UF rates are associated with lower rates of intradialytic hypotension and less myocardial ischemia on cardiac imaging. Oral loop diuretics are one potential strategy to increase urine output and reduce volume-associated complications in HD patients. Observational data show associations between loop diuretic use and lower IDWG, less intradialytic hypotension and fewer hospitalizations. Diuretics may represent a pragmatic, low-cost strategy to improve outcomes in HD patients. However, lack of data on optimal dosing, safety, and acceptability are barriers to expanded use. To fill this knowledge gap and generate preliminary data necessary for a subsequent clinical trial, we propose an 18-week open label, pilot feasibility study to test if escalating doses of furosemide are safe, well tolerated, and effective at increasing urine volume in HD patients. In an initial 6-week dose-titration period (Aim 1), we will evaluate the short-term safety and efficacy of escalating oral furosemide doses in 36 HD patients with residual urine output. In a subsequent 12-week follow-up period (Aim 2), we will evaluate the longer-term patient acceptance of and adherence to furosemide, and the longer-term safety and efficacy of furosemide. The valuable data generated from this pilot study will: 1) identify potential barriers to recruitment, 2) inform optimal furosemide dose selection and titration, and 3) provide key safety data, all essential factors in determining the merit of a larger trial. Pilot data will also inform power calculations necessary to design an R01-level clinical trial that will test if furosemide reduces volume-related complications in HD patients.
Hemodialysis patients experience a disproportionately high burden of complications and death from cardiovascular causes. Volume-related factors such as volume overload and more rapid fluid removal during dialysis contribute to these adverse outcomes. In this project, we will study furosemide (a ?water pill? that increases urine output) to learn if it is safe, well tolerated and effective at increasing urine output in hemodialysis patients, important information to help us design a future, larger clinical trial of furosemide.