Urinary Chloride-to-Creatinine Ratio as an Early Predictor of Diuretic Resistance in Acute Heart Failure

Abstract

Background: Diuretic resistance is an important issue in the management of acute heart failure, as it is associated with slow decongestive response and high likelihood of ongoing fluid retention, renal failure and longer hospital stays. The aim of this study was to assess the usefulness of the urinary chloride to creatinine ratio as an early predictor for inadequate diuretic response.

Methods: This is a prospective, observational study of 110 adults hospitalized at Mayo Hospital Lahore with acute heart failure from April 2025 to April 2026. Spot urine was done two hours following the first dose of intravenous Furosemide. Diuretic resistance was considered to be low urine output on 24-hour basis, poor weight loss and intensification of diuretic therapy. ROC analysis and multivariable logistic regression were undertaken.

Results: Diuretic resistance occurred in 35 patients (31.8%). The median urinary chloride to creatinine ratio was significantly lower in resistant compared to responsive patients (56 [38-72] vs 118 [86-156] mmol/g, p<0.001). A cut-off of < 72 mmol/g was shown to have 82.9% sensitivity, 78.7% specificity, and an area under the curve of 0.86 for predicting resistance. A ratio <72 mmol/g was independently associated with resistance after the adjustment (adjusted odds ratio 6.18; 95% confidence interval 2.43–15.69; p<0.001). Resistant patients were also less likely to have high urine output, less net fluid loss, more worsening renal function, persistent congestion, and shorter hospital stay. After adjustment for kidney function, systolic blood pressure, chronic use of a loop diuretic, serum chloride and sex, the association was still present, suggesting that it is independently predictive in routine clinical practice settings.

Conclusion: Urinary chloride to creatinine ratio is a fast, simple, and clinically helpful method of rapid assessment of early diuretic resistance in acute heart failure.