Journal
KIDNEY INTERNATIONAL
Volume 98, Issue 5, Pages 1210-1224Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2020.05.043
Keywords
anemia; chronic kidney disease; FGF23; gene expression; mineral metabolism; pediatric nephrology; phosphate
Categories
Funding
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK114558, R01DK095112, RO1DK090554-07]
- National Center for Advancing Translational Sciences [UL1TR002384]
- National Heart, Lung, and Blood Institute [R01 HL133801]
- Rohr Family Clinical Scholar Award
- [KL2TR002385]
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Anemia is a frequent complication of chronic kidney disease (CKD), related in part to the disruption of iron metabolism. Iron therapy is very common in children with CKD and excess iron has been shown to induce bone loss in non-CKD settings, but the impact of iron on bone health in CKD remains poorly understood. Here, we evaluated the effect of oral and parenteral iron therapy on bone transcriptome, bone histology and morphometry in two mouse models of juvenile CKD (adenine-induced and 5/6-nephrectomy). Both modalities of iron therapy effectively improved anemia in the mice with CKD, and lowered bone Fgf23 expression. At the same time, iron therapy suppressed genes implicated in bone formation and resulted in the loss of cortical and trabecular bone in the mice with CKD. Bone resorption was activated in untreated CKD, but iron therapy had no additional effect on this. Furthermore, we assessed the relationship between biomarkers of bone turnover and iron status in a cohort of children with CKD. Children treated with iron had lower levels of circulating biomarkers of bone formation (bone-specific alkaline phosphatase and the amino-terminal propeptide of type 1 procollagen), as well as fewer circulating osteoblast precursors, compared to children not treated with iron. These differences were independent of age, sex, and glomerular filtration rate. Thus, iron therapy adversely affected bone health in juvenile mice with CKD and was associated with low levels of bone formation biomarkers in children with CKD.
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