Erythropoietic response and outcomes in kidney disease and type 2 diabetes
Open accessAbstract
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.)
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In pre-dialysis CKD patients with or without diabetes, higher Hgb targets, particularly in patients with poor initial Hgb responses, were associated with increased cardiovascular risk.
“In pre-dialysis CKD patients with or without diabetes higher Hgb targets, particularly in patients with poor initial Hgb responses, were also associated with increased cardiovascular risk.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [230]
In pre-dialysis CKD patients with or without diabetes, higher Hgb targets, particularly in patients with poor initial Hgb responses, were associated with increased cardiovascular risk.
“In pre-dialysis CKD patients with or without diabetes higher Hgb targets, particularly in patients with poor initial Hgb responses, were also associated with increased cardiovascular risk.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [231]
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- Authors
- Solomon, S. D., Uno, H., Lewis, E. F., Eckardt, K.-U., Lin, J., Burdmann, E. A., de Zeeuw, D., Ivanovich, P., Levey, A. S., Parfrey, P., Remuzzi, G., Singh, A. K., Toto, R., Huang, F., Rossert, J., McMurray, J. J. V., & Pfeffer, M. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Faculdade de Medicina de São José do Rio Preto (BR)
- Northwestern University (US)
- Tufts Medical Center (US)
- St. John’s Health Sciences Centre (CA)
- Mario Negri Institute for Pharmacological Research (IT)
- The University of Texas Southwestern Medical Center (US)
- Amgen (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2010-09-16
- Volume
- 363
- Issue
- 12
- Pages
- 1146-1155
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2046224330
- Cited by
- 473
- References
- 23
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 16 · 2023: 25 · 2022: 32 · 2021: 30 · 2020: 28 · 2019: 28 · 2018: 22 · 2017: 21 · 2016: 28 · 2015: 26 · 2014: 37 · 2013: 44 · 2012: 48
- FWCI
- 30.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- erythropoiesis-stimulating agents, darbepoetin alfa, chronic kidney disease, type 2 diabetes, anemia, hemoglobin response, erythropoietic response, hemoglobin target, cardiovascular events, mortality, non-dialysis patients
- MeSH terms
- Darbepoetin alfa, Aged, Anemia, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Erythropoietin, Female, Hematinics, Hemoglobins, Humans, Injections, Subcutaneous, Kidney Failure, Chronic, Male, Middle Aged, Risk, Chi-Square Distribution, Proportional Hazards Models, Stroke
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