Urinary Biomarker Thresholds to Detect Diuretic Resistance and Insufficient Diuretic Response in Acute Heart Failure

AIMS: Early identification of poor diuretic response is central to acute heart failure (AHF) care, yet the recommended post-diuretic urine sodium (uNa+) thresholds are neither prospectively derived nor validated. We aimed to derive and validate clinically actionable urinary biomarker thresholds to identify poor diuretic response. METHODS AND RESULTS: In this prospective derivation-validation study, 336 AHF patients formed the derivation cohort, and 141 patients formed the validation cohort. Spot urinary biomarkers were measured 2h after loop diuretic administration. Diuretic resistance was defined as urine output <500 mL/6 h, and insufficient diuretic response as <1000 mL/6 h. In the derivation cohort, optimal uNa thresholds were <60 mmol/L and <90 mmol/L, respectively. For diuretic resistance, uNa+ <60 mmol/L showed 0.80 (95%CI: 0.65 -0.90) sensitivity, 0.94 (95%CI: 0.90-0.96) specificity, and an area under the curve (AUC) of 0.93 (95%CI: 0.90-0.97). For insufficient diuretic response, uNa+ <90 mmol/L showed 0.80 (95%CI: 0.69-0.86) sensitivity, 0.84 (95%CI: 0.787-0.878) specificity, and an AUC of 0.86 (95%CI: 0.83-0.93). In the validation cohort, uNa+ <60 mmol/L had numerically higher sensitivity than uNa+ <50 mmol/L (0.87 (95%CI: 062 -0.98) vs. 0.73 (95%CI: 0.48- 0.89)), with similar specificity (0.94 (95%CI: 0.89 -0.97) vs. 0.97 (95%CI: 0.92-0.99)) for diuretic resistance. For insufficient diuretic response, uNa+ <90 mmol/L had higher sensitivity: 0.86 (95%CI: 0.71-0.94) than lower thresholds, with specificity: 0.83 (95%CI: 0.75 -0.89). CONCLUSIONS: In AHF, data-derived post-diuretic uNa+ thresholds of <60 mmol/L and <90 mmol/L identify diuretic resistance and insufficient diuretic response, respectively. Further research and broad external validation are needed.