Erythropoietic response and outcomes in kidney disease and type 2 diabetes

Solomon, Scott D., Uno, Hajime, Lewis, Eldrin F., Eckardt, Kai-Uwe, Lin, Julie, Burdmann, Emmanuel A., de Zeeuw, Dick, Ivanovich, Peter, Levey, Andrew S., Parfrey, Patrick, Remuzzi, Giuseppe, Singh, Ajay K., Toto, Robert, Huang, Fannie, Rossert, Jerome, McMurray, John J.V., Pfeffer, Marc A., Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Investigators and Johnson, David W. (2010) Erythropoietic response and outcomes in kidney disease and type 2 diabetes. The New England Journal of Medicine, 363 12: 1146-1155. doi:10.1056/NEJMoa1005109

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Author Solomon, Scott D.
Uno, Hajime
Lewis, Eldrin F.
Eckardt, Kai-Uwe
Lin, Julie
Burdmann, Emmanuel A.
de Zeeuw, Dick
Ivanovich, Peter
Levey, Andrew S.
Parfrey, Patrick
Remuzzi, Giuseppe
Singh, Ajay K.
Toto, Robert
Huang, Fannie
Rossert, Jerome
McMurray, John J.V.
Pfeffer, Marc A.
Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Investigators
Johnson, David W.
Title Erythropoietic response and outcomes in kidney disease and type 2 diabetes
Journal name The New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2010-09-16
Sub-type Article (original research)
DOI 10.1056/NEJMoa1005109
Volume 363
Issue 12
Start page 1146
End page 1155
Total pages 10
Place of publication United States
Publisher Massachusetts Medical Society
Collection year 2011
Language eng
Formatted abstract
Non-placebo-controlled trials of erythropoiesis-stimulating agents (ESAs) comparing lower and higher hemoglobin targets in patients with chronic kidney disease indicate that targeting of a lower hemoglobin range may avoid ESA-associated risks. However, target-based strategies are confounded by each patient's individual hematopoietic response.

We assessed the relationship among the initial hemoglobin response to darbepoetin alfa after two weight-based doses, the hemoglobin level achieved after 4 weeks, the subsequent darbepoetin alfa dose, and outcomes in 1872 patients with chronic kidney disease and type 2 diabetes mellitus who were not receiving dialysis. We defined a poor initial response to darbepoetin alfa (which occurred in 471 patients) as the lowest quartile of percent change in hemoglobin level (<2%) after the first two standardized doses of the drug.

Patients who had a poor initial response to darbepoetin alfa had a lower average hemoglobin level at 12 weeks and during follow-up than did patients with a better hemoglobin response (a change in hemoglobin level ranging from 2 to 15% or more) (P<0.001 for both comparisons), despite receiving higher doses of darbepoetin alfa (median dose, 232 μg vs. 167 μg; P<0.001). Patients with a poor response, as compared with those with a better response, had higher rates of the composite cardiovascular end point (adjusted hazard ratio, 1.31; 95% confidence interval [CI], 1.09 to 1.59) or death (adjusted hazard ratio, 1.41; 95% CI, 1.12 to 1.78).

A poor initial hematopoietic response to darbepoetin alfa was associated with an increased subsequent risk of death or cardiovascular events as doses were escalated to meet target hemoglobin levels. Although the mechanism of this differential effect is not known, these findings raise concern about current target-based strategies for treating anemia in patients with chronic kidney disease. (Funded by Amgen; number, NCT00093015.) Copyright © 2010 Massachusetts Medical Society.
Keyword Aged
Cardiovascular diseases
Chi-square distribution
Diabetes mellitus
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
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Created: Wed, 23 Mar 2011, 09:10:47 EST by Debbie Banks on behalf of School of Medicine