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

Abstract

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.

The role of urine chloride in acute heart failure

“…While uNa + has received substantial attention as an indicator of resistance to diuretic treatment and worsening HF symptoms leading to increased mortality 28 – 30 , uCl − has been overlooked as a valuable biomarker, despite its significant role in HF pathophysiology 31 . Most previous studies regarding Cl − have primarily focused on serum concentration 7 , and to the best of our knowledge, our study is among the few to explore the relationship between uCl − and patient outcomes 32 , 33 . Our analysis of urine biomarkers reveals a positive correlation between all analyzed electrolytes, consistent with trends observed in serum levels.…”

Serum Chloride Is Inversely Associated With 3 Months Outcomes in Chinese Patients With Heart Failure, a Retrospective Cohort Study

“…However, hypochloremia in turn induces renin secretion, increases the expression and activity of sodium-potassium-chloride cotransporters as well as sodium-chloride cotransporters, and promotes electrolytes reabsorption leading to diuretic resistance ( 25 ). Several studies have demonstrated that low serum chloride is apparently associated with neurohormonal activation and diuretic resistance, leading to impaired decongestive diuretic efficacy in patients with heart failure, which in turn increases the risk of death and readmission ( 26 , 27 ). This may be a common consequence of hypochloremia.…”