Document Detail


Erythropoietic response and outcomes in kidney disease and type 2 diabetes.
MedLine Citation:
PMID:  20843249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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; ClinicalTrials.gov number, NCT00093015.)
Authors:
Scott D Solomon; Hajime Uno; Eldrin F Lewis; Kai-Uwe Eckardt; Julie Lin; Emmanuel A Burdmann; Dick de Zeeuw; Peter Ivanovich; Andrew S Levey; Patrick Parfrey; Giuseppe Remuzzi; Ajay K Singh; Robert Toto; Fannie Huang; Jerome Rossert; John J V McMurray; Marc A Pfeffer;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  363     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-09-23     Revised Date:  2011-06-02    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1146-55     Citation Subset:  AIM; IM    
Affiliation:
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02114, USA. ssolomon@rics.bwh.harvard.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00093015
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MeSH Terms
Descriptor/Qualifier:
Aged
Anemia / drug therapy*,  etiology
Cardiovascular Diseases / epidemiology,  prevention & control
Chi-Square Distribution
Diabetes Mellitus, Type 2 / blood,  complications*,  mortality
Double-Blind Method
Erythropoietin / analogs & derivatives*,  therapeutic use
Female
Hematinics / therapeutic use*
Hemoglobins / metabolism*
Humans
Injections, Subcutaneous
Kidney Failure, Chronic / blood,  complications*,  mortality
Male
Middle Aged
Proportional Hazards Models
Risk
Stroke / epidemiology
Chemical
Reg. No./Substance:
0/Hematinics; 0/Hemoglobins; 11096-26-7/Erythropoietin; 209810-58-2/darbepoetin alfa
Comments/Corrections
Comment In:
Am J Kidney Dis. 2011 May;57(5):661-3   [PMID:  21411198 ]
N Engl J Med. 2011 Jan 27;364(4):385; author reply 385-6   [PMID:  21268743 ]
N Engl J Med. 2011 Jan 27;364(4):384; author reply 385-6   [PMID:  21268746 ]
N Engl J Med. 2011 Jan 27;364(4):384-5; author reply 385-6   [PMID:  21268744 ]
N Engl J Med. 2011 Jan 27;364(4):384; author reply 385-6   [PMID:  21268745 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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