title: Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France. jp7ferreira@hotmail.com.|Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal. jp7ferreira@hotmail.com.
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Ferreira
authors.affiliation: INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girerd
authors.affiliation: Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Pedro Bettencourt
authors.initials: PB
authors.lastname: Medeiros
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal.|Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Santos
authors.affiliation: Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Henrique Cyrne
authors.initials: HC
authors.lastname: Carvalho
authors.affiliation: Centro Hospitalar São João, Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Bettencourt
authors.affiliation: Service de cardiologie, hôpital E.-Muller, 20, rue du Docteur-Laennec, BP 1070, 68070, Mulhouse Cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Kénizou
authors.affiliation: Division of Cardiology, Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: INSERM, Centre D'Investigations Cliniques 1433, INSERMU116, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, 4 Rue du Morvan, Vandoeuvre lès Nancy, 54500, Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D005260:Female; D005602:France; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000652:urine; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015999:Multivariate Analysis; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012964:Sodium / Q000652:urine*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D049994:Sodium Potassium Chloride Symporter Inhibitors; D013148:Spironolactone; D012964:Sodium; D011188:Potassium
keywords: Acutely decompensated heart failure; Outcomes; Spironolactone; Spot urinary sodium