Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure

Abstract

Background: Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose.

Methods and results: We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r(2)≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04-1.78; P=0.02; ESCAPE: HR, 2.86; 95% CI, 1.53-5.36; P=0.001).

Conclusions: Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Keywords: cardio-renal syndrome; diuresis; diuretic; heart failure; survival.

Figure 1

Distribution of diuretic efficiency in the Penn and ESCAPE cohorts

Figure 2

Scatterplots of eGFR and net fluid output, diuretic dose (Panel A) and diuretic efficiency (Panel B) in the Penn Cohort (top panels) and ESCAPE cohort (bottom panels) eGFR: Estimated glomerular filtration rate. Diuretic efficiency expressed as mL of net fluid output per 40 mg of furosemide equivalent.

Figure 2

Scatterplots of eGFR and net fluid output, diuretic dose (Panel A) and diuretic efficiency (Panel B) in the Penn Cohort (top panels) and ESCAPE cohort (bottom panels) eGFR: Estimated glomerular filtration rate. Diuretic efficiency expressed as mL of net fluid output per 40 mg of furosemide equivalent.

Figure 2

Scatterplots of eGFR and net fluid output, diuretic dose (Panel A) and diuretic efficiency (Panel B) in the Penn Cohort (top panels) and ESCAPE cohort (bottom panels) eGFR: Estimated glomerular filtration rate. Diuretic efficiency expressed as mL of net fluid output per 40 mg of furosemide equivalent.

Figure 2

Scatterplots of eGFR and net fluid output, diuretic dose (Panel A) and diuretic efficiency (Panel B) in the Penn Cohort (top panels) and ESCAPE cohort (bottom panels) eGFR: Estimated glomerular filtration rate. Diuretic efficiency expressed as mL of net fluid output per 40 mg of furosemide equivalent.

Figure 3

Kaplan-Meier survival curves grouped by diuretic efficiency and diuretic dose in the Penn cohort (Panel A) and ESCAPE cohort (Panel B) Loop diuretic dose and diuretic efficiency were dichotomized into high and low by the median value in each cohort. “Low loop dose” was also defined as a loop diuretic dose above or below the median value which was 280 mg (120–600) in the Penn cohort and 240 mg in 24 hours (120–400) in the ESCAPE cohort.

Figure 3

Kaplan-Meier survival curves grouped by diuretic efficiency and diuretic dose in the Penn cohort (Panel A) and ESCAPE cohort (Panel B) Loop diuretic dose and diuretic efficiency were dichotomized into high and low by the median value in each cohort. “Low loop dose” was also defined as a loop diuretic dose above or below the median value which was 280 mg (120–600) in the Penn cohort and 240 mg in 24 hours (120–400) in the ESCAPE cohort.