BACKGROUND: Hepcidin regulates iron homeostasis by blocking iron absorption from the gut and iron release from macrophage and hepatocyte stores. Hepcidin levels are elevated in kidney failure and thus, are thought to contribute to dysregulation of iron homeostasis in chronic kidney disease (CKD). However, the primary factors associated with increased hepcidin levels in CKD patients have not been well-defined. In particular, few studies examined the relationships between hepcidin and disorders of mineral metabolism, which are among the earliest and most common complications of CKD. METHODS: We examined the associations between hepcidin, iron indexes, and markers of mineral metabolism in 125 patients from across the spectrum of pre-dialysis CKD. Bioactive hepcidin levels were measured in serum samples by competitive ELISA. RESULTS: Hepcidin was inversely associated with eGFR and linearly associated with ferritin (p < 0.001 for both). In unadjusted analyses, increased serum phosphate and parathyroid hormone (PTH) and decreased 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were associated with increased hepcidin. When examined in forward stepwise regression analysis, higher phosphate and PTH levels and lower 1,25(OH)2D and FGF23 levels were selected as independent predictors of higher hepcidin levels, whereas there was no association between eGFR and hepcidin. CONCLUSIONS: Abnormalities in phosphate and vitamin D metabolism were associated with increased hepcidin levels independently of eGFR in CKD patients. These findings suggest that disorders of mineral metabolism may promote increased hepcidin secretion in CKD. Whether inflammation mediates these associations requires further study.
BACKGROUND:Hepcidin regulates iron homeostasis by blocking iron absorption from the gut and iron release from macrophage and hepatocyte stores. Hepcidin levels are elevated in kidney failure and thus, are thought to contribute to dysregulation of iron homeostasis in chronic kidney disease (CKD). However, the primary factors associated with increased hepcidin levels in CKDpatients have not been well-defined. In particular, few studies examined the relationships between hepcidin and disorders of mineral metabolism, which are among the earliest and most common complications of CKD. METHODS: We examined the associations between hepcidin, iron indexes, and markers of mineral metabolism in 125 patients from across the spectrum of pre-dialysis CKD. Bioactive hepcidin levels were measured in serum samples by competitive ELISA. RESULTS:Hepcidin was inversely associated with eGFR and linearly associated with ferritin (p < 0.001 for both). In unadjusted analyses, increased serum phosphate and parathyroid hormone (PTH) and decreased 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were associated with increased hepcidin. When examined in forward stepwise regression analysis, higher phosphate and PTH levels and lower 1,25(OH)2D and FGF23 levels were selected as independent predictors of higher hepcidin levels, whereas there was no association between eGFR and hepcidin. CONCLUSIONS: Abnormalities in phosphate and vitamin D metabolism were associated with increased hepcidin levels independently of eGFR in CKDpatients. These findings suggest that disorders of mineral metabolism may promote increased hepcidin secretion in CKD. Whether inflammation mediates these associations requires further study.
Authors: Meredith A Atkinson; Michal L Melamed; Juhi Kumar; Cindy N Roy; Edgar R Miller; Susan L Furth; Jeffrey J Fadrowski Journal: J Pediatr Date: 2013-10-08 Impact factor: 4.406
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Authors: Oleh Akchurin; Angara Sureshbabu; Steve B Doty; Yuan-Shan Zhu; Edwin Patino; Susanna Cunningham-Rundles; Mary E Choi; Adele Boskey; Stefano Rivella Journal: Am J Physiol Renal Physiol Date: 2016-07-20
Authors: Carrie E Thomas; Ronnie Guillet; Ruth A Queenan; Elizabeth M Cooper; Tera R Kent; Eva K Pressman; Francoise M Vermeylen; Mark S Roberson; Kimberly O O'Brien Journal: Am J Clin Nutr Date: 2015-10-07 Impact factor: 7.045