Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort

Abstract

Background: Hepcidin, a key iron regulatory protein, is elevated in patients with chronic kidney disease (CKD). Its role in the development and progression of the anemia of CKD in children remains poorly defined.

Methods: Cross-sectional and longitudinal study in children aged 1-16 years with stage 2-4 CKD in the Chronic Kidney Disease in Children (CKiD) cohort (n = 133) with hepcidin measured at baseline and hemoglobin (HGB) measured annually at follow-up. Anemia was defined as HGB <5th percentile for age/sex OR treatment with an erythropoiesis-stimulating agent (ESA).

Results: Hepcidin levels correlated negatively with glomerular filtration rate (GFR; r = -0.22, p = 0.01) and positively with ferritin (r = 0.67, p < 0.001). At the lower end of the GFR spectrum at baseline (10th percentile, 27.5 mL/min/1.73 m(2)), higher hepcidin was associated with a 0.87 g/dL decrease in HGB during follow-up (95 % CI -1.69, -0.05 g/dL, p = 0.038). At higher GFR percentiles there was no significant association between baseline hepcidin and HGB during follow-up. Among 90 non-anemic subjects at baseline, 23.3 % developed incident anemia. In subjects with GFR ≤ the median, a higher hepcidin level was associated with an increased risk of incident anemia (at the 10th percentile GFR, HR 3.471, 95 % CI 1.228, 9.810, p = 0.019; at the 25th percentile GFR, HR 2.641, 95 % CI 1.213, 5.750, p = 0.014; at the 50th percentile GFR, HR 1.953, 95 % CI 1.011, 3.772, p = 0.046). Among subjects with GFR at the 75th percentile or above, incrementally higher baseline hepcidin was not associated with increased anemia risk.

Conclusions: Higher hepcidin levels are associated with a decreased HGB and an increased risk of incident anemia, and this association is most significant among subjects with lower GFR.

Conflict of interest statement

Conflict of interest disclosure for Cindy N. Roy, PhD: CNR was the Principal Investigator for a sponsored research agreement between Johns Hopkins University and the Celgene Corporation from 2011–2012.

Figures

Figure 1

Scatter plots of (a) log-transformed serum hepcidin vs GFR (mL/min/1.73m2);(b) HGB (g/dL) vs log(hepcidin) among 133 children; (c) log serum hepcidin (ng/mL) vs serum ferritin (ng/mL); (d) ranks of hepcidin and ferritin among 63 children.