Clinical Significance of Spot Urinary Chloride Concentration Measurements in Patients with Acute Heart Failure: Investigation on the Basis of the ‘TubuloGlomerular Feedback’ Mechanism

Urinary chloride (Cl) is the key electrolyte for regulating renin secretion at the macula densa under the ‘tubulo-glomerular feedback’. Whether or not Cl filtrated into the urinary tubules actually associates with plasma renin activity (PRA) in clinical heart failure (HF) remains unclear. Data from 29 patients with acute worsening HF (48% men; 80.3±12 years) were analyzed. Blood and urine samples were immediately obtained before decongestive therapy after the patients rested in a supine position for 20-min. Clinical tests included peripheral blood tests, serum and spot urinary electrolytes, b-type natriuretic peptide (BNP), plasma neurohormones, and fractional urinary electrolyte excretion. In the 29 patients, urinary Cl concentrations inversely correlated with logarithmically transformed PRA (R2 =0.41, p=0.0002). The correlation was weaker in worsening chronic HF patients (R2 =0.32, p=0.01) compared with de novo HF patients (R2 =0.70, p=0.0026). Patients were divided into 2 groups according to the median urinary Cl concentration, a low group and a high group. Compared with the high group (100~184 mEq/L; n=14), the low group (4~95 mEq/L; n=15) exhibited more renal (serum creatinine; 1.45±0.63 vs 1.00±0.38 mg/d, p=0.029) and cardiac (log BNP; 2.99±0.3 vs 2.66±0.32 pg/mL, p=0.008 p=0.008) impairment, and higher PRA (3.42±4.7 vs 0.73±0.46 ng/mL/h, p=0.049), and lower fractional excretion of urinary Cl (1.34±1.3 vs 5.33±4.1%, p<0.0001). The present study provides clinical data on the possible functioning of urinary Cl involved in the mechanism of ‘tubulo-glomerular feedback’, and thus advances our understanding of the clinical meanings of the significance of urinary Cl concentration measurement.