title: Changes in renal function during hospitalization and soon after discharge in patients admitted for worsening heart failure in the placebo group of the EVEREST trial.
abstract: OBJECTIVE
  To provide an in-depth clinical characterization and analysis of outcomes of the patients hospitalized for heart failure (HF) who subsequently develop worsening renal function (WRF) during hospitalization or soon after discharge.
  
  
  RESULTS
  Of the 4133 patients hospitalized with worsening HF and reduced left ventricular ejection fraction (LVEF) (≤40%) in the EVEREST trial, 2072 were randomized to tolvaptan, a selective vasopressin-2 receptor antagonist, and 2061 were randomized to placebo, both in addition to standard therapy. This analysis included the 2021 (98%) patients in the placebo group with a complete set of renal function parameters. Renal function parameters and clinical variables were measured prospectively during hospitalization and after discharge. Worsening renal function was defined as an increase in sCr ≥0.3 mg/dL during the in-hospital (randomization to discharge or Day 7) and post-discharge (discharge or Day 7 to 4 weeks post-discharge) periods. Blood pressure (BP), body weight (BW), natriuretic peptides (NPs), and congestion score were correlated with WRF. The prognostic value of baseline renal function at admission and WRF during hospitalization and post-discharge on long-term outcomes were assessed using a Cox proportional hazards model adjusted for other baseline covariates. At randomization, 53.2% of patients had moderately or severely reduced estimated glomerular filtration rate (eGFR) (<60.0 mL/min/1.73 m2). Worsening renal function was observed in 13.8% in-hospital and 11.9% post-discharge. Worsening renal function during hospitalization and post-discharge was associated with greater reductions in BP, BW, and NPs. Baseline renal dysfunction as well as in-hospital and post-discharge WRF were predictive of a composite endpoint of cardiovascular (CV) mortality/HF rehospitalization.
  
  
  CONCLUSIONS
  The prevalence of renal dysfunction is high in patients hospitalized for HF with reduced LVEF. Worsening renal function may occur not only during hospitalization, but also in the early post-discharge period. Since worsening renal function during hospitalization is associated with a significant decrease in signs and symptoms of congestion, body weight and natriuretic peptides, which are good prognostic indicators, worsening renal function during hospitalization as an endpoint in clinical trials should be re-evaluated.
authors.affiliation: Wilford Hall Medical Center, San Antonio, TX,  USA.
authors.forename: John E A
authors.initials: JE
authors.lastname: Blair
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pang
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Brian
authors.initials: B
authors.lastname: Traver
authors.forename: Thomas
authors.initials: T
authors.lastname: Cook
authors.forename: Umberto
authors.initials: U
authors.lastname: Campia
authors.forename: Andrew
authors.initials: A
authors.lastname: Ambrosy
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Liliana
authors.initials: L
authors.lastname: Grinfeld
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D059347:Cardio-Renal Syndrome / Q000209:etiology* / Q000503:physiopathology; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000502:physiology; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D013318:Stroke Volume / Q000502:physiology; D000077602:Tolvaptan; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan