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In heart failure (HF), renal dysfunction (RD) is associated with reduced survival; however, evidence indicates that that not all causes of RD are prognostically equivalent. Notably, the risk attributable to a reduced estimated glomerular filtration rate (eGFR) is largely restricted to patients with an elevated blood urea nitrogen to creatinine ratio (BUN/Cr; a surrogate for “pre-renal” physiology such as HF-induced RD). Independent of eGFR, proteinuria has also been associated with adverse events. Proteinuria can also be caused by several different mechanisms and a “functional” form of proteinuria induced by renal neurohormonal activation (i.e., “pre-renal” physiology) has been well described.
Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) trial limited dataset with urinary protein assessed at baseline (dipstick) were studied (n=6,520). All survival models were fully adjusted for baseline characteristics, including eGFR.
Proteinuria (trace or 1+) was present in 26% of the population and associated with increased mortality (HR=1.2, 95% CI 1.1-1.3, p=0.004). Proteinuria ≥2+ was less common (2.5%) but demonstrated a stronger relationship with mortality (HR=1.9, 95% CI 1.5-2.4, p<0.0001). In patients with a BUN/Cr in the top tertile (≥17.3), both any (HR=1.4, 95% CI 1.1-1.6, p=0.001) and ≥2+ proteinuria (HR=2.0, 95% CI 1.4-2.8, p<0.0001) were associated with increased mortality. However, in patients with a BUN/Cr in the bottom tertile (≤13.3), any proteinuria (HR=1.0, 95% CI 0.8-1.2, p=0.96, p interaction= 0.006) and ≥2+ proteinuria (HR=1.3, 95% CI 0.8-2.1, p=0.27, p interaction=0.06) were not associated with significantly worsened survival.
Analogous to a reduced eGFR, the mechanism underlying proteinuria may be important in determining the associated survival disadvantage. Additional research is necessary to better understand and characterize different phenotypes of RD in HF.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.-4:30 p.m.
Session Title: New Paradigms in Prognostic Role of Biomarkers in Heart Failure
Abstract Category: 15. Heart Failure: Clinical
Presentation Number: 1265-312
- 2013 American College of Cardiology Foundation