A Pathophysiological Role of Plasma Indoxyl Sulfate in Patients with Heart Failure

Abstract

Background: One of uremic toxins, indoxyl sulfate (IS), is associated with cardiovascular events. This study aimed to measure the plasma IS levels in patients with and without chronic heart failure (CHF). Methods: We measured plasma IS levels in 49 patients with CHF and an estimated glomerular filtration rate (eGFR) of 40–60 ml/min/1.73 m2 from our institute. These were compared with 31 healthy subjects without CHF (a control), but with comparable eGFR levels, from our resident cohort study. We also test the effect of AST-120 (the oral adsorbent) in 16 CHF patients. Results: The plasma IS levels in 49 CHF patients increased (1.38 ± 0.84 (SD) vs 0.12 ± 0.07 μg/ml (a control), p < 0.001), and fractional shortening (FS) levels were correlated with the plasma IS levels in these subjects. Second, in our database of the hospitalized CHF patients, we retrospectively reviewed the data for eight CHF patients with stage 3–5 chronic kidney disease (CKD) who received treatment with AST-120, before and one year after treatment, and compared these patients with eight sex-matched CHF patients with stage 3–5 CKD without AST-120. AST-120 decreased plasma IS levels and improved cardiac function. Conclusions: Plasma IS levels increased in patients with CHF along with cardiac systolic dysfunction compared with those in healthy subjects, and AST-120 improved cardiac dysfunction in patients with CHF. Oral adsorbents may represent a novel treatment for CHF.

Keywords

• AST-120
• cardiovascular hemodynamics
• heart failure
• indoxyl sulfate