The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio.
Pubmed ID: 27153048
Pubmed Central ID: PMC4986924
Journal: International journal of cardiology
Publication Date: July 15, 2016
MeSH Terms: Humans, Male, Female, Aged, Risk Factors, Middle Aged, Survival Analysis, Randomized Controlled Trials as Topic, Heart Failure, Prognosis, Renal Insufficiency, Glomerular Filtration Rate, Ventricular Dysfunction, Left, Enalapril, Blood Urea Nitrogen, Proteinuria
Grants: K23 HL114868, L30 HL115790, K23 HL128933, K23 DK097201, UL1 TR001863, R01 HL123478
Authors: Testani JM, Zile MR, Brisco MA, Hanberg JS, Ter Maaten JM, Wilson FP, Parikh C
Cite As: Brisco MA, Zile MR, Ter Maaten JM, Hanberg JS, Wilson FP, Parikh C, Testani JM. The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio. Int J Cardiol 2016 Jul 15;215:521-6. Epub 2016 Apr 14.
Studies:
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. METHODS AND 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. CONCLUSION: Analogous to a reduced eGFR, the mechanism underlying proteinuria in HF may be important in determining the associated survival disadvantage.