Endogenous sodium-potassium-chloride cotransport inhibitor in congestive heart failure

Objectives. This study sought to evaluate the relation, if any, between fluid overload in congestive heart failure (CHF) and newly discovered endogenous natriuretic factor acting like loop diuretic drugs: contransport inhibitory factor (CIF). Background. The humoral mechanisms regulating volume overload in CHF are not fully understood. Therefore, we investigated whether there is role for CIF in this pathologic condition. Methods. Plasm and urinary CIF levels were investigated in 23 patients with chronic CHF and compared with changes in plasm atrial natriuretic peptide (ANP). Twelve patients without CHF served as control subjects. Results. CHF was associated with highly significant threefold increase in both plasm CIF levels (mean ± SD 7.10 ± 3.01 vs. 2.28 ± 0.92 U/ml, p < 0.0001) and urinary CIF excretion (7,849 ± 3,600 vs. 2,351 ± 1,297 U/day, p < 0.0001) with respect to patients without CHF. CIF increased as function of impairment in left ventricular ejection fraction (r = −0.703, p < 0.0001) and the severity of clinical status. Plasm ANP was also increased in patients with CHF, although to lesser extent (68%, P = 0.0501) than plasm CIF, and was also significantly correlated with left ventricular ejection fraction (r = −0.552, P = 0.0004). Conclusions. Plasm and urinary CIF activities were strongly and very significantly increased in chronic CHF. In addition to ANP, this long-term natriuretic agent may be of potential importance in reducing fluid overload in CHF.