Normalization of hemoglobin level in patients with chronic kidney disease and anemia.
BACKGROUND
Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established.


METHODS
We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease.


RESULTS
During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1.


CONCLUSIONS
In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919 [ClinicalTrials.gov].).
Drüeke
Tilman B
TB
Inserm Unité 507 and Assistance Publique-Hôpitaux de Paris, Necker Hospital, Division of Nephrology, Paris, France. drueke@necker.fr
Locatelli
Francesco
F
Clyne
Naomi
N
Eckardt
Kai-Uwe
KU
Macdougall
Iain C
IC
Tsakiris
Dimitrios
D
Burger
Hans-Ulrich
HU
Scherhag
Armin
A
D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D018450:Disease Progression; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011994:Recombinant Proteins; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000401:mortality; D016019:Survival Analysis
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin