title: The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio.
abstract: BACKGROUND
  Renal dysfunction (RD) is associated with reduced survival in HF; however, not all RD is mechanistically or prognostically equivalent. Notably, RD associated with "pre-renal" physiology, as identified by an elevated blood urea nitrogen to creatinine ratio (BUN/Cr), identifies a particularly high risk RD phenotype. Proteinuria, another domain of renal dysfunction, has also been associated with adverse events. Given that several different mechanisms can cause proteinuria, we sought to investigate whether the mechanism underlying proteinuria also affects survival in HF.
  
  
  RESULTS
  Subjects in the Studies of Left Ventricular Dysfunction (SOLVD) trial with proteinuria assessed at baseline were studied (n=6439). All survival models were adjusted for baseline characteristics and estimated glomerular filtration rate (eGFR). Proteinuria (trace or 1+) was present in 26% and associated with increased mortality (HR=1.2; 95% CI, 1.1-1.3, p=0.006). Proteinuria >1+ was less common (2.5%) but demonstrated a stronger relationship with mortality (HR=1.9; 95% CI, 1.5-2.5, p<0.001). In patients with BUN/Cr in the top tertile (≥17.3), any proteinuria (HR=1.3; 95% CI, 1.1-1.5, p=0.008) and >1+ proteinuria (HR=2.3; 95% CI, 1.7-3.3, p<0.001) both remained associated with mortality. However, in patients with BUN/Cr in the bottom tertile (≤13.3), any proteinuria (HR=0.95; 95% CI, 0.77-1.2, p=0.63, p interaction=0.015) and >1+ proteinuria (HR=1.3; 95% CI, 0.79-2.2, p=0.29, p interaction=0.036) were not associated with worsened survival.
  
  
  CONCLUSIONS
  Analogous to a reduced eGFR, the mechanism underlying proteinuria in HF may be important in determining the associated survival disadvantage.
authors.affiliation: Department of Medicine, Cardiology Division, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Brisco
authors.affiliation: Department of Medicine, Cardiology Division, Medical University of South Carolina, Charleston, South Carolina, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: Department of Cardiology, University Medical Center Groningen, the Netherlands.
authors.forename: Jozine M
authors.initials: JM
authors.lastname: Ter Maaten
authors.affiliation: Program of Applied Translational Research, Yale University, New Haven, Connecticut, United States.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hanberg
authors.affiliation: Program of Applied Translational Research, Yale University, New Haven, Connecticut, United States.
authors.forename: F Perry
authors.initials: FP
authors.lastname: Wilson
authors.affiliation: Program of Applied Translational Research, Yale University, New Haven, Connecticut, United States.
authors.forename: Chirag
authors.initials: C
authors.lastname: Parikh
authors.affiliation: Program of Applied Translational Research, Yale University, New Haven, Connecticut, United States. Electronic address: jeffrey.testani@yale.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Testani
mesh_terms: D000368:Aged; D001806:Blood Urea Nitrogen; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000097:blood / Q000503:physiopathology*; D012307:Risk Factors; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left
chemical_list: D004656:Enalapril
keywords: Albuminuria; Blood urea nitrogen to creatinine ratio; Cardiorenal syndrome; Heart failure; Proteinuria