Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect

Clin Res Cardiol. 2016 Jun;105(6):489-507. doi: 10.1007/s00392-015-0945-x. Epub 2015 Nov 28.

Abstract

Introduction: Loop diuretic resistance characterized by inefficient sodium excretion complicates many patients with acutely decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) in natriuretic doses may improve spot urine sodium excretion and outcomes.

Objective: Our primary aim was to assess the association of high-dose spironolactone with short-term spot urine sodium excretion, and our secondary aim was to determine if this higher short-term spot urine sodium excretion is associated with reduction in the composite clinical outcome (of cardiovascular mortality and/or ADHF hospitalization) event rate at 180 days.

Methods: Single-centre, non-randomized, open-label study enrolling 100 patients with ADHF. Patients were treated with standard ADHF therapy alone (n = 50) or oral spironolactone 100 mg/day plus standard ADHF therapy (n = 50). Spot urine samples were collected at day 1 and day 3 of hospitalization.

Results: Spironolactone group had significantly higher spot urine sodium levels compared to standard care group at day 3 (84.13 ± 28.71 mmol/L vs 70.74 ± 34.43 mmol/L, p = 0.04). The proportion of patients with spot urinary sodium <60 mmol/L was lower in spironolactone group at day 3 (18.8 vs 45.7, p = 0.01). In multivariate analysis, spironolactone was independently associated with increased spot urinary sodium and urinary sodium/potassium ratio of >2 at day 3 (both, p < 0.05). Higher spot urine sodium levels were associated with a lower event rate [HR for urinary sodium >100 mmol/L = 0.16 (0.06-0.42), p < 0.01, compared to <60], and provided a significant prognostic gain measured by net reclassification indexes.

Conclusion: Spot urinary sodium levels >60 mmol/L and urinary sodium/potassium ratio >2 measured at day 3 of hospitalization for ADHF are associated with improved mid-term outcomes. Spironolactone is associated with increased spot urinary sodium and sodium/potassium ratio >2.

Keywords: Acutely decompensated heart failure; Outcomes; Spironolactone; Spot urinary sodium.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Chi-Square Distribution
  • Female
  • France
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Heart Failure / urine
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Multivariate Analysis
  • Natriuresis / drug effects*
  • Potassium / urine
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sodium / urine*
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Spironolactone / adverse effects
  • Spironolactone / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Urinalysis

Substances

  • Biomarkers
  • Mineralocorticoid Receptor Antagonists
  • Sodium Potassium Chloride Symporter Inhibitors
  • Spironolactone
  • Sodium
  • Potassium