An Abnormal Apelin/Vasopressin Balance May Contribute to Water Retention in Patients With the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and Heart Failure

Context: Apelin and vasopressin levels are regulated in opposite directions to maintain body fluid homeostasis. Objective: We thus assessed plasma apelin to copeptin ratios, with plasma copeptin concentrations as a reliable index of vasopressin secretion, in pathological states combining high levels of vasopressin secretion with hyponatremia. Design, Participants, and Setting: We carried out a cross-sectional study including 113 healthy subjects, 21 hyponatremic patients with the syndrome of inappropriate antidiuretic hormone (SIADH), and 16 normonatremic and 16 hyponatremic patients with chronic heart failure (CHF) in an academic hospital. Outcome Measures: Individual apelin to copeptin ratios were plotted against natremia and compared with those of 10 healthy subjects of a previous study acutely challenged by water loading or hypertonic saline infusion. We calculated the percentage of SIADH/CHF patients whose apelin to copeptin ratio for a given natremia lies outside the 95% prediction limits of the physiological relationship. Results: In healthy subjects, median (interquartile range) plasma apelin and copeptin concentrations were 254 fmol/mL (225-311) and 4.0 fmol/mL (2.6-6.9), respectively. Sex-and age-adjusted plasma apelin concentrations were 26% higher in SIADH and normonatremic and hyponatremic CHF patients than in healthy subjects. Sex-and age-adjusted plasma copeptin concentration was 75%, 187%, and 207% higher in SIADH and normonatremic and hyponatremic CHF patients, respectively, than in healthy subjects. During an acute osmotic challenge, the plasma apelin to copeptin ratio decreased exponentially with natremia. Apelin to copeptin ratios as a function of natremia were outside the 95% predicted physiological limits for 86% of SIADH patients and 81% of hyponatremic CHF patients. Conclusion: Inappropriate apelin concentrations and apelin to copeptin ratios as a function of natremia in SIADH and CHF patients suggest that the increase in plasma apelin secretion cannot compensate for the higher levels of vasopressin release and may contribute to the corresponding water metabolism defect.