Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.
Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Carlo A
CA
Gaillard
Department of Nephrology, Kantonsspital, Aarau, Switzerland.
Andreas H
AH
Bock
Department of Dialysis, Eurodial, DaVita, Leiria, Portugal.
Fernando
F
Carrera
Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.
Kai-Uwe
KU
Eckardt
Clinical Support Services, Davita Healthcare Partners, Denver, CO, United States of America.
David B
DB
Van Wyck
Institute of Pharmaceutical Science, King's College, London, United Kingdom.
Sukhvinder S
SS
Bansal
Vifor Pharma Ltd, Glattbrugg, Switzerland.
Maureen
M
Cronin
Vifor Pharma Ltd, Glattbrugg, Switzerland.
Yvonne
Y
Meier
Vifor Pharma Ltd, Glattbrugg, Switzerland.
Sylvain
S
Larroque
Renal Research, Gosford, NSW, Australia.
Simon D
SD
Roger
Department of Renal Medicine, King's College Hospital, London, United Kingdom.
Iain C
IC
Macdougall
D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D005293:Ferritins / Q000097:blood; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000008:administration & dosage; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D013997:Time Factors
D005290:Ferric Compounds; C578702:HAMP protein, human; D064451:Hepcidins; C522335:ferric carboxymaltose; D008320:Maltose; D005293:Ferritins; D007501:Iron