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
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