The Utility of Urine Biomarkers in Diuretic Resistance Prediction in Heart Failure Hospitalization

AIMS: Loop diuretic resistance (LDR) in patients with heart failure hospitalization (HHF) is associated with worse clinical outcomes. The study aimed to assess the predictive ability of urine biomarkers for LDR in HHF. METHODS: Consecutive patients with congestive HHF were included. Congestion was defined as the presence of oedema, ascites, or pleural effusion. LDR was defined as persistent congestion on the fourth day of hospitalization despite high intravenous loop diuretic doses. Urine biomarkers [Kidney Injury Molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), uromodulin, glutathione S-transferase Pi (pi-GST) and aquaporin-2], transthoracic echocardiography (TTE), clinical and biochemical parameters on the first and fourth days of hospital stay were evaluated. RESULTS: Forty patients were included. Median age was 84 years (72.8; 86), a median left ventricle ejection fraction (EF) 35.3% (26.5; 49) and a median NT-proBNP 8967.5 pg/mL (3.024; 15.241). LDR was identified in 14 (35%) patients. Univariate analysis identified risk factors for LDR: urine pi-GST concentration on admission and on the fourth day, right ventricle-to-pulmonary circulation coupling index (TAPSE/PASP ratio), serum creatinine and total cholesterol concentrations. Multivariable regression analysis identified that only the urine pi-GST was a significant independent risk factor for LDR. The area under the receiver operating characteristic (ROC) curve (AUC) to predict LDR using urine pi-GST concentration was 0.713 [95% confidence interval (CI), 0.552-0.874; P = 0.009], with 50% sensitivity and 84% specificity. CONCLUSIONS: Urine pi-GST concentration may serve as a marker for the development of LDR in patients with HF hospitalization.