Prognostic values of proteinuria in patients with acute heart failure

Yuka Akama; Yuya Matsue; Daichi Maeda; Taishi Dotare; Tsutomu Sunayama; Takashi Iso; Yudai Fujimoto; Taisuke Nakade; Shoichiro Yatsu; Sayaki Ishiwata; Yutaka Nakamura; Shoko Suda; Takao Kato; Masaru Hiki; Takatoshi Kasai; Tohru Minamino

doi:10.1016/j.jjcc.2025.01.010

Prognostic values of proteinuria in patients with acute heart failure

J Cardiol. 2025 Jan 28:S0914-5087(25)00010-3. doi: 10.1016/j.jjcc.2025.01.010. Online ahead of print.

Authors

Affiliations

¹ Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
² Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: yuya8950@gmail.com.
³ Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁴ Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, Japan.

PMID: 39884428
DOI: 10.1016/j.jjcc.2025.01.010

Abstract

Background: Renal dysfunction is significantly associated with poor prognosis in patients with heart failure. However, the prognostic significance of proteinuria as a potential marker of an impaired glomerular filtration barrier in acute heart failure (AHF) remains unclear. We aimed to investigate the prognostic value of urinary protein/creatinine ratio (PCR) in patients with AHF.

Methods: Urinary protein levels measured at admission were adjusted for urinary creatinine concentrations in 346 patients (75 ± 13 years; 61 % men) with AHF. Patients were categorized based on urinary PCR, adhering to the Japanese chronic kidney disease (CKD) guideline cut-offs for CKD staging: A1 (<0.15 g/gCr), A2 (0.15-0.49 g/gCr), and A3 (≥0.5 g/gCr). The primary endpoint was all-cause mortality.

Results: Overall, there were 85, 126, and 135 patients in the A1, A2, and A3 groups, respectively. Groups A2 and A3 were associated with lower hemoglobin levels, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide levels, and poor renal function. Moreover, groups A2 and A3 had high cystatin C, alpha 1 microglobulin, and urinary liver-type fatty acid-binding protein (L-FABP) levels. Urinary PCR correlated more with tubular markers, alpha 1-microglobulin, and L-FABP than with the glomerular marker cystatin C. Over a median follow-up period of 434 (interquartile range: 89-753) days, 72 deaths occurred. Elevated urinary PCR was associated with higher mortality rates (log-rank test, p < 0.001), even after adjusting for other variables [A2 vs. A1: hazard ratio (HR) 2.59, 95 % confidence interval (CI) 0.71-9,55, p = 0.15; A3 vs. A1: HR 4.40, 95 % CI 1.17-16.6, p = 0.029].

Conclusions: Elevated urinary PCR is more prevalent in patients with AHF and is associated with a higher risk of all-cause mortality, independent of covariates, including glomerular function. Thus, urinary PCR at admission should provide prognostic information independent of glomerular function.

Keywords: Glomerular function; Heart failure; Proteinuria; Renal dysfunction; Urinary protein/creatinine ratio.