Italian randomized trial of hemoglobin maintenance to prevent or delay left ventricular hypertrophy in chronic kidney disease.
BACKGROUND
This study is part of a 3-country study testing whether normal levels of hemoglobin (Hgb) delay the progression of left ventricular (LV) growth in chronic kidney disease (CKD) patients not on dialysis.


METHODS
This was an open-label, randomized, multicenter, controlled trial conducted in 27 tertiary-care hospitals in Italy. Treated subjects (n=46) received epoetin-alpha (EPO-alpha) to maintain Hgb levels in the range 12-14 g/dL. Control subjects (n=49) were not treated unless their Hgb decreased to 9.0 g/dL. Primary outcome was LV mass index (MI) change after 24 months. Subcutaneous EPO-alpha was withdrawn in Europe and the study prematurely terminated; therefore, a 12-month analysis was carried out.


RESULTS
Mean age was 57 years (38% were women, 18% with diabetes, 76% taking ACEI or ARB and 22% statins). EPO-alpha median final dose was 2,000 IU/week. Hgb significantly increased (12.4 -/+ 1.1 g/L) for the treatment group and decreased for controls (11.3 -/+ 1.3 g/L; p<0.001). The intention-to-treat analysis was conducted in 78 patients. Mean baseline LVMI for treated patients and controls was 109.5 -/+ 23 g/m2 and 108.7 -/+ 29 g/m2, respectively. LVMI did not change among controls, whereas it decreased slightly, though not significantly, among treated patients.


CONCLUSIONS
The current Italian trial was negative, maybe due to its limitations: lack of power, 1-year follow-up and normal LVMI in some patients at start; however, it was consistent with other published studies. Thus, it is unlikely that targeting hemoglobin in the normal range for CKD patients is of benefit.
Cianciaruso
Bruno
B
Division of Nephrology, Faculty of Medicine, University "Federico II" of Naples, Naples - Italy. cianciar@unina.it
Ravani
Pietro
P
Barrett
Brendan J
BJ
Levin
Adeera
A
D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D007558:Italy; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa