FO016HEPCIDIN RESPONSE TO IRON THERAPY IN PATIENTS WITH NON-DIALYSIS CKD: AN ANALYSIS OF THE FIND-CKD TRIAL

Abstract

Introduction and Aims: Hepcidin is the master regulator of iron availability in the body. The longitudinal response of this peptide to iron therapy has not been examined, nor are there any data comparing the short‐ or long‐term hepcidin response to oral vs intravenous (IV) iron. Methods: FIND‐CKD was a 56‐week, open‐label, multicentre, prospective, randomised study of 626 anaemic patients with non‐dialysis CKD (ND‐CKD) and iron deficiency not receiving ESA therapy. Patients were randomised (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400‐600μg/L) or lower (100‐200μg/L) ferritin, or oral iron. In a subpopulation of 61 patients enrolled in the UK, serum hepcidin was measured centrally at baseline and at months 1, 2, 3, 6, 9 and 12 by a validated liquid chromatography tandem mass spectrometry assay. Results: Baseline hepcidin levels were broadly similar to the normal range for healthy individuals (0‐6ng/mL). Mean hepcidin increased significantly from baseline by week 4 in both the high and low ferritin FCM groups, and remained significantly higher vs baseline thereafter; however, the increase was greater with high ferritin vs low ferritin FCM at all time points. The increase in hepcidin vs baseline with oral iron was similar to that seen with low ferritin FCM from week 4 onwards. The least squares mean (SE) change from baseline to end of study was significantly higher in the high ferritin FCM vs the oral iron group ( p<0.001; ANCOVA, last observation carried forward [LOCF]) (Table 1). Ferritin correlated significantly with hepcidin at all time points (baseline r=0.432, p<0.001; end of study r=0.645, p<0.001) in the overall study population (Figure). Conclusions: These data from a prospective, randomised trial with extended follow‐up provide the first robust data elucidating the three‐way relationship between iron therapy, ferritin and hepcidin in ND‐CKD. Results show that hepcidin levels rise in response to iron therapy, regardless of route of administration. The magnitude of the hepcidin rise is directly related to the level of ferritin achieved. (Figure Presented).