Proposal for New Classification and Practical Use of Diuretics According to Their Effects on the Serum Chloride Concentration: Rationale Based on the “Chloride Theory”

Currently, diuretic therapy for heart failure (HF) pathophysiology is primarily focused on the sodium and water balance. Over the last several years, however, chloride (Cl) has been recognized to have an important role in HF pathophysiology, as both a prognostic marker and a possible central factor regulating the body fluid status. I recently proposed a unifying hypothesis for HF pathophysiology, called the "chloride theory", during HF worsening and recovery, as follows. Chloride is the key electrolyte for regulating both reabsorption of tubular electrolytes and water in the kidney through the renin-angiotensin-aldosterone system and distributing body fluid in each compartment of the body. As changes between the serum Cl concentration and plasma volume are intimately associated with worsening HF and its recovery after decongestive therapy, modulation of the serum Cl concentration by careful selection and combination of various diuretics and their doses could become an attractive therapeutic option for HF. In this review, I will propose a new classification and practical use of diuretics according to their effects on the serum Cl concentration. Diuretic use according to this classification is expected to be a useful strategy for the treatment of patients with HF.