• David J Webb, Blai Coll, Hiddo J L Heerspink, Dennis Andress, Yili Pritchett, John J Brennan, Mark Houser, Ricardo Correa-Rotter, Donald Kohan, Hirofumi Makino, Vlado Perkovic, Giuseppe Remuzzi, Sheldon W Tobe, Robert Toto, Robert Busch, Pablo Pergola, Hans-Henrik Parving, and Dick de Zeeuw.
• Edinburgh Hypertension Excellence Centre, Clinical Pharmacology Unit, University of Edinburgh, E3.22, QMRI, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK. D.J.Webb@ed.ac.uk.
• Drugs R D. 2017 Sep 1; 17 (3): 441-448.

BackgroundFluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan.ObjectiveWe performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately reflected fluid retention during treatment with atrasentan.Study DesignWe conducted a randomized, double-blind, placebo-controlled study in 48 patients with type 2 diabetes mellitus and nephropathy who were receiving stable doses of renin angiotensin system inhibitors and diuretics.MethodsPatients were randomized 1:1:1 to placebo, atrasentan 0.5 mg, or atrasentan 1.25 mg once daily for 8 weeks. Thoracic bioimpedance, vital signs, clinical exams, and serologies were taken at weeks 1, 2, 4, 6, and 8, with the exception of serum hemoglobin, which was not taken at week 1, and serum brain natriuretic peptide, which was only taken at baseline, week 4, and week 8.ResultsAlterations in bioimpedance were more often present in those who received atrasentan than in those who received placebo, though overall differences were not statistically significant. Transient declines in thoracic bioimpedance during the first 2 weeks of atrasentan exposure occurred before or during peak increases in body weight and hemodilution (decreased serum hemoglobin).ConclusionsWe conclude that thoracic bioimpedance did not reflect changes in weight gain or edema with atrasentan treatment in this study. However, the sample size was small, and it may be of interest to explore the use of thoracic bioimpedance in a larger population to understand its potential clinical use in monitoring fluid retention in patients with chronic kidney disease who receive ET receptor antagonists.

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