Prognostic values of proteinuria in patients with acute heart failure

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.

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.

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].

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.