Meta-analysis: Erythropoiesis-stimulating agents in patients with chronic kidney disease

Palmer, Suetonia C., Navaneethan, Sankar D., Craig, Jonathan C., Johnson, David W., Tonelli, Marcello, GargMd, Amit X., Pellegrini, Fabio, Ravani, Pietro, Jardine, Meg, Perkovic, Vlado, Graziano, Giusi, McGee, Richard, Nicolucci, Antonio, Tognoni, Gianni and Strippoli, Giovanni F. M. (2010) Meta-analysis: Erythropoiesis-stimulating agents in patients with chronic kidney disease. Annals of Internal Medicine, 153 1: 23-W23.

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Author Palmer, Suetonia C.
Navaneethan, Sankar D.
Craig, Jonathan C.
Johnson, David W.
Tonelli, Marcello
GargMd, Amit X.
Pellegrini, Fabio
Ravani, Pietro
Jardine, Meg
Perkovic, Vlado
Graziano, Giusi
McGee, Richard
Nicolucci, Antonio
Tognoni, Gianni
Strippoli, Giovanni F. M.
Title Meta-analysis: Erythropoiesis-stimulating agents in patients with chronic kidney disease
Journal name Annals of Internal Medicine   Check publisher's open access policy
ISSN 0003-4819
Publication date 2010-07
Sub-type Critical review of research, literature review, critical commentary
Volume 153
Issue 1
Start page 23
End page W23
Total pages 22
Place of publication Philadelphia, PA, USA
Publisher American College of Physicians
Collection year 2011
Language eng
Formatted abstract
Background: Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease (CKD) increases the risk for death. Additional randomized trials have been recently completed.

To summarize the effects of ESA treatment on clinical outcomes in patients with anemia and CKD.

Data Sources:
MEDLINE (January 1966 to November 2009), EMBASE (January 1980 to November 2009), and the Cochrane database (to March 2010) were searched without language restriction.

Study Selection: Two authors independently screened reports to identify randomized trials evaluating ESA treatment in people with CKD. Hemoglobin target trials or trials of ESA versus no treatment or placebo were included.

Data Extraction: Two authors independently extracted data on patient characteristics, study risks for bias, and the effects of ESA therapy.

Data Synthesis: 27 trials (10 452 patients) were identified. A higher hemoglobin target was associated with increased risks for stroke (relative risk [RR], 1.51 [95% CI, 1.03 to 2.21]), hypertension (RR, 1.67 [CI, 1.31 to 2.12]), and vascular access thrombosis
(RR, 1.33 [CI, 1.16 to 1.53]) compared with a lower hemoglobin target. No statistically significant differences in the risks for mortality (RR, 1.09 [CI, 0.99 to 1.20]), serious cardiovascular events (RR, 1.15 [CI, 0.98 to 1.33]), or end-stage kidney disease (RR, 1.08 [CI, 0.97 to 1.20]) were observed, although point estimates favored a lower hemoglobin target. Treatment effects were consistent across subgroups, including all stages of CKD.

Limitations: The evidence for effects on quality of life was limited by selective reporting. Trials also reported insufficient information to allow analysis of the independent effects of ESA dose on clinical outcomes.

Conclusion: Targeting higher hemoglobin levels in CKD increases risks for stroke, hypertension, and vascular access thrombosis and probably increases risks for death, serious cardiovascular events, and end-stage renal disease. The mechanisms for harm remain unclear, and meta-analysis of individual-patient data and trials on
fixed ESA doses are recommended to elucidate these mechanisms.
Copyright © 2011 Elsevier B.V. All rights reserved.
Keyword Recombinant human erythropoietin
Chronic renal failure
Treated hemodialysis patients
Randomized controlled trial
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Faculty of Health and Behavioural Sciences -- Publications
Official 2011 Collection
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Citation counts: TR Web of Science Citation Count  Cited 127 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 18 Jul 2010, 00:10:14 EST