Association between BUN to creatinine ratio, ultrasonographic congestion and neurohormonal activation in outpatients with heart failure

Background. Blood urea nitrogen to serum creatinine ratio (BUN/sCr) is considered a marker of neurohormonal activation related to arterial underfilling, and therefore as a guide to taper or withdraw diuretic treatment. However, the association between BUN/sCr and prognosis is stronger in patients with heart failure with preserved ejection fraction (HFpEF), who are known to exhibit a reduced neurohormonal activation as compared with patients with heart failure and a reduced ejection fraction (HFrEF); moreover, kidney dysfunction in HF is increasingly recognized to be due to backward failure (i.e. venous congestion) than to forward failure (i.e. impaired cardiac output). The aim of this study was to assess the relationship between BUN/sCr, ultrasonographic congestion and neurohormonal activation in outpatients with heart failure. Methods. We studied 473 consecutive patients with HF; we performed a complete echocardiographic exam, comprehensive of venous and pulmonary congestion evaluation, three-dimensional echocardiography, and a thorough biohumoral assessment. We elaborated a congestion score consisting of increased inferior vena cava (IVC) diameter, discontinuous renal venous flow (RVF), and increased lung B-lines. Study population was divided in tertiles according to BUN/sCr. Results. Patients with higher levels of BUN/sCr displayed a significantly increased ultrasonographic congestion (P = 0.021) and a more pronounced neurohormonal activation, indicated by renin and aldosterone levels (renin: 26.4, interquartile range [IQR] 9.2-71.3, mIU/L in the highest tertile vs 14.1, IQR 4.6-38.9, mUI/L in the lowest tertile, P = 0.013; aldosterone: 3.2, IQR 8.7-18.3, ng/dL vs 10.1, IQR 6.5-15.0, ng/dL). When examining single items of congestion score, only discontinuous RVF reached statistical significance (P=0.031), with higher BUN/sCr being associated with a more impaired RVF. Conclusion. Higher levels of BUN/sCr are associated with systemic venous congestion, in particular with impaired renal venous flow, and with enhanced neurohormonal activation. The decision to taper or withdraw diuretic treatment cannot be taken without thorough and seriated ultrasonographic assessments of congestion.