Change in hemoglobin trajectory and darbepoetin dose approaching end-stage renal disease: data from the trial to reduce cardiovascular events with aranesp therapy trial

Mc Causland, F. R. et al. (2017) Change in hemoglobin trajectory and darbepoetin dose approaching end-stage renal disease: data from the trial to reduce cardiovascular events with aranesp therapy trial. American Journal of Nephrology, 46(6), pp. 488-497. (doi: 10.1159/000485326) (PMID:29241199)

Abstract

Background: The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). Methods: We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. Results: Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI –1.26 to –1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of follow-up. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were >140 μg/L and 20%, respectively. Conclusions: Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1–2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP.

• Item Type: Articles
• Additional Information: The TREAT Study was funded by Amgen. Dr. Finnian R. Mc Causland is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK102511.
• Keywords: Anemia, C-reactive protein end-stage renal disease type 2 diabetes mellitus, chronic kidney disease, hemoglobin.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Mc Causland, F. R., Claggett, B., Pfeffer, M. A., Burdmann, E. A., Eckardt, K.-U., Levey, A. S., McMurray, J. J.V., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., and Parfrey, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Nephrology
• Publisher: Karger Publishers
• ISSN: 0250-8095
• ISSN (Online): 1421-9670
• Published Online: 14 December 2017
• Copyright Holders: Copyright © 2017 S. Karger AG
• First Published: First published in American Journal of Nephrology 46(6): 488-497
• Publisher Policy: Reproduced in accordance with the publisher copyright policy