Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial


Por: Webb D.J., Coll B., Heerspink H.J.L., Andress D., Pritchett Y., Brennan J.J., Houser M., Correa-Rotter R., Kohan D., Makino H., Perkovic V., Remuzzi G., Tobe S.W., Toto R., Busch R., Pergola P., Parving H.-H., de Zeeuw D.

Publicada: 1 ene 2017
Categoría: Pharmacology

Resumen:
Background: Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan. Objective: We 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 Design: We 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. Methods: Patients 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. Results: Alterations 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). Conclusions: We 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. © 2017, The Author(s).

Filiaciones:
Webb D.J.:
 Edinburgh Hypertension Excellence Centre, Clinical Pharmacology Unit, University of Edinburgh, E3.22, QMRI, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom

Coll B.:
 AbbVie, North Chicago, IL, United States

Heerspink H.J.L.:
 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands

Andress D.:
 AbbVie, North Chicago, IL, United States

Pritchett Y.:
 MedImmune, Gaithersburg, MD, United States

Brennan J.J.:
 AbbVie, North Chicago, IL, United States

Houser M.:
 AbbVie, North Chicago, IL, United States

Correa-Rotter R.:
 National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico

Kohan D.:
 University of Utah Health Sciences Center, Salt Lake City, UT, United States

Makino H.:
 Okayama University Graduate School of Medicine, Okayama, Japan

Perkovic V.:
 The University of Sydney, Sydney, NSW, Australia

Remuzzi G.:
 Azienda Ospedaliera Papa Giovanni XXIII and IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy

Tobe S.W.:
 Sunnybrook Health Sciences Center, Toronto, ON, Canada

Toto R.:
 University of Texas Southwestern Medical Center, Dallas, TX, United States

Busch R.:
 The Endocrine Group, New York, NY, United States

Pergola P.:
 Renal Associates, P.A, San Antonio, TX, United States

Parving H.-H.:
 University Hospital of Copenhagen, Copenhagen, Denmark

de Zeeuw D.:
 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
ISSN: 11745886
Editorial
Springer International Publishing
Tipo de documento: Article
Volumen: 17 Número: 3
Páginas: 441-448
WOS Id: 000412499300013
ID de PubMed: 28831752

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