Maintenance of elevated versus physiological iron indices in non-anaemic patients with chronic kidney disease: a randomized controlled trial.
BACKGROUND
An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD).


METHODS
One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment.


RESULTS
Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups.


CONCLUSIONS
Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L.
McMahon
Lawrence P
LP
Department of Renal Medicine, Eastern Health, Melbourne, Victoria, Australia. lawrence.mcmahon@easternhealth.org.au
Kent
Annette B
AB
Kerr
Peter G
PG
Healy
Helen
H
Irish
Ashley B
AB
Cooper
Bruce
B
Kark
Adrian
A
Roger
Simon D
SD
D000284:Administration, Oral; D000368:Aged; D000740:Anemia / Q000517:prevention & control*; D002908:Chronic Disease; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077605:Ferric Oxide, Saccharated; D005293:Ferritins / Q000097:blood; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D005937:Glucaric Acid; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012720:Severity of Illness Index
D005290:Ferric Compounds; D005296:Ferrous Compounds; D006397:Hematinics; D006454:Hemoglobins; C020748:ferrous sulfate; D005293:Ferritins; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid