Prognostic Value of Glomerular Filtration Changes Versus Natriuretic Response in Decompensated Heart Failure With Reduced Ejection FREDERIK HENDRIK VERBRUGGE, MD, 1,2 PETRA NIJST, MD, 1,2 MATTHIAS DUPONT, MD, 1 CARMEN REYNDERS, MSc, 3 JORIS PENDERS, MD, PhD, 3,4 W.H. WILSON TANG, MD, 5 AND WILFRIED MULLENS, MD, PhD 1,4 Genk and Diepenbeek, Belgium; and Cleveland, Ohio ABSTRACT Background: Glomerular filtration rate (GFR) and natriuretic response to diuretics represent important treatment targets in acute decompensated heart failure (ADHF). Methods and Results: Consecutive ADHF patients (n 5 50) with ejection fraction #45% and clinical signs of volume overload received protocol-driven decongestive therapy. Serum creatinine (Cr), cystatin C (CysC), and b-trace protein (bTP) were measured on admission and three subsequent days of treat- ment. Worsening renal function (WRF) was defined as a $0.3 increase in absolute biomarker levels or $20% decrease in estimated GFR. Consecutive 24-hour urinary collections were simultaneously per- formed to measure Cr clearance and natriuresis. Serum Cr, CysC, and bTP were strongly correlated at admission (r 5 0.788e0.909) and during decongestive treatment (r 5 0.884e888). Moreover, derived GFR estimates correlated well with Cr clearance (r 5 0.820e0.908). Nevertheless, WRF inci- dence differed markedly according to Cr- (26%e30%), CysC- (46%e54%), or bTP-based definitions (31%e48%). WRF by any definition was not associated with all-cause mortality or ADHF readmission, in contrast to stronger natriuresis per loop diuretic dose [hazard ratio 0.20 (95% confidence interval 0.06e0.64); P 5 .007]. Conclusions: Serial measurements of CysC/bTP, compared with serum Cr, more frequently indicate WRF during decongestive treatment in ADHF. However, adverse clinical outcome in such patients might be better predicted by the natriuretic response to diuretic therapy. (J Cardiac Fail 2014;20:817e824) Key Words: Glomerular filtration rate, congestive heart failure, natriuresis. Renal function has traditionally been appraised by the ability of the kidneys to achieve glomerular filtration. Glomerular filtration rate (GFR) is a strong predictor of all-cause mortality in both chronic and acute decompen- sated heart failure (ADHF), outperforming left ventricular ejection fraction and New York Heart Association func- tional class in this respect. 1,2 Despite some well known lim- itations, such as analytic assay variability, secretion by the proximal tubules, and dependency on muscle mass, diet, and physical activity, widespread availability allows serum creatinine (Cr) to serve as the major biomarker to estimate GFR. 3e6 Recently, serum cystatin C (CysC) and b-trace protein (bTP) have been proposed as alternatives with potentially fewer shortcomings. At the population level in ADHF, admission values of CysC or bTP portend stronger prognostic value compared with serum Cr. 7 Therefore, From the 1 Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; 2 Doctoral School for Medicine and Life Sciences, Hasselt Uni- versity, Diepenbeek, Belgium; 3 Department of Laboratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium; 4 Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium and 5 Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Manuscript received June 13, 2014; revised manuscript received July 28, 2014; revised manuscript accepted August 7, 2014. Reprint requests: Wilfried Mullens, MD, PhD, Department of Cardiol- ogy, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium. Tel: þ32 89 32 70 87; Fax: þ32 89 32 79 18. E-mail: wilfried. mullens@zol.be Funding: Frederik Verbrugge is supported by a PhD fellowship from the Research FoundationeFlanders (FWO, 11L8214N). Frederik Verbrugge, Petra Nijst, and Wilfried Mullens are researchers for the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the Lim- burg Sterk Merk foundation, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. See page 823 for disclosure information. 1071-9164/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2014.08.002 817 Journal of Cardiac Failure Vol. 20 No. 11 2014