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

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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 m2), 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.

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Acknowledgements

The authors would like to thank Christopher Pierce, MHS, and Alison Abraham, PhD for their valuable assistance in the design of the statistical analysis. Data in this manuscript were collected by the Chronic Kidney Disease in Children Prospective Cohort (CKiD) Study with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri Kansas City (Bradley Warady, MD) and the Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and the data coordinating center (Alvaro Muñoz, PhD) at the Johns Hopkins Bloomberg School of Public Health.

Support

The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01DK-082194, U01-DK-66116). The CKID website is located at http://www.statepi.jhsph.edu/ckid. Meredith Atkinson MD, MHS, was supported by the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; K23-DK-084116). At the Johns Hopkins University School of Medicine, Dr Atkinson was also supported by grant number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Cindy N. Roy PhD was supported by R01 DK082722. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of NIDDK, NCRR or NIH.

Conflict of interest

Cindy N. Roy, PhD, was the Principal Investigator for a sponsored research agreement between Johns Hopkins University and the Celgene Corporation from 2011 to 2012.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Baltimore, MD, 21287, USA

    Meredith A. Atkinson

  2. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Ji Young Kim & Susan L. Furth

  3. Divisions of Hematology and Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Cindy N. Roy

  4. Children’s Mercy Hospital, Kansas City, MO, USA

    Bradley A. Warady

  5. British Columbia Children’s Hospital, Vancouver, BC, Canada

    Colin T. White

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  1. Meredith A. Atkinson
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  2. Ji Young Kim
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  3. Cindy N. Roy
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  6. Susan L. Furth
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Correspondence to Meredith A. Atkinson.

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Atkinson, M.A., Kim, J.Y., Roy, C.N. et al. Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol 30, 635–643 (2015). https://doi.org/10.1007/s00467-014-2991-4

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  • DOI: https://doi.org/10.1007/s00467-014-2991-4

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