Targeting Higher Hemoglobin Levels in Chronic Kidney Disease Linked to Worse Outcomes
By Laurie Barclay, MD
Medscape Medical News
May 4, 2010 — Targeting higher hemoglobin levels in chronic kidney disease (CKD) is linked to worse outcomes, according to the results of a systematic review reported early release May 3 in the Annals of Internal Medicine.
"Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in ...CKD increases the risk for death," write Suetonia C. Palmer, MB, ChB, from the University of Otago, Christchurch, New Zealand, and colleagues. "Additional randomized trials have been recently completed."
The goal of this review was to determine the effects of ESA treatment on clinical outcomes in patients with anemia and CKD. The investigators searched MEDLINE from January 1966 to November 2009, EMBASE from January 1980 to November 2009, and the Cochrane database to March 2010 for appropriate articles, without language restriction. Randomized hemoglobin target trials or trials of ESA vs no treatment or with placebo were independently identified by 2 authors, who also independently extracted data on patient characteristics, study risks for bias, and the effects of ESA treatment.
The reviewers identified 27 trials, enrolling a total of 10,452 patients. Compared with a lower hemoglobin target, a higher hemoglobin target was associated with greater risks for stroke (relative risk [RR], 1.51; 95% confidence interval [CI], 1.03 - 2.21), hypertension (RR, 1.67; 95% CI, 1.31 - 2.12), and vascular access thrombosis (RR, 1.33; 95% CI, 1.16 - 1.53).
There was a nonsignificant trend favoring a lower hemoglobin target in risks for mortality (RR, 1.09; 95% CI, 0.99 - 1.20), serious cardiovascular events (RR, 1.15; 95% CI, 0.98 - 1.33), and end-stage kidney disease (RR, 1.08; 95% CI, 0.97 - 1.20). Various subgroups, including those based on different stages of CKD, showed consistent treatment effects.
Limitations of this review include selective reporting of effects on quality of life and insufficient information reported in trials to permit analysis of the independent effects of ESA dose on clinical outcomes.
"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 review authors write. "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."
This review had no external funding. Some of the study authors have disclosed various financial relationships with Amgen, Roche, Janssen-Cilag, Sandoz, the University of Western Ontario, and/or the Italian Agency for Drugs.
