In:
Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
Abstract:
Iron (Fe) deficiency significantly contributes to anemia in chronic kidney disease (CKD). High FGF23 levels, commonly found in CKD, are related to adverse outcomes in patients. In the normal setting, an association between Fe deficiency and FGF23 has been observed. However, it is unknown whether Fe deficiency-induced anemia might contribute to the excessive FGF23 levels in CKD. Thus, this study was intended to evaluate the interplay between Fe deficiency, CKD, and FGF23. Method Male Wistar rats with normal renal function received either standard (40 ppm Fe) or Fe-deficient (4 ppm Fe) diets for 6 weeks to induce anemia. Then, several normal and all the anemic rats were switched to an adenine-enriched (0.6%) diet to induce renal damage. Groups of anemic-uremic animals were treated with oral (ferric citrate, FC and ferrous sulfate, FS) or intravenous (ferric carboxymaltose, FCx) Fe at a dose of 9 mg/kg for 5 weeks. Hematological and mineral metabolism parameters were determined at sacrifice. All experimental protocols were approved by the Ethics Committee for Animal Research of the University of Córdoba. Results Plasma and serum biochemistries are shown in Table 1. CKD per se was associated with derangements in hematological parameters. The presence of Fe deficiency-induced anemia further decreased these parameters, being statistically significant in the case of serum Fe (P = 0.003). Iron therapy improved hematocrit, hemoglobin, and Fe levels, although statistical significance for all of them was only reached when FC was administered (P = 0.012, P = 0.038, and P = 0.002, respectively). As expected, CKD rats exhibited disturbances in mineral metabolism. Interestingly, uremic and anemic rats showed higher intact (P = 0.039) and c-terminal (P = 0.048) FGF23 levels when compared with CKD group. Despite normalization of serum Fe, intact FGF23 further increased following administration of FS (P = 0.022), and same trend was observed with all the compounds. However, cFGF23 levels remained unchanged in all the Fe-treated groups. Conclusion The presence of Fe-induced anemia in an experimental model of CKD is associated with further increases in the levels of both intact and c-terminal FGF23. Thus, other factors distinct than serum Fe might influence FGF23 levels. Our results support the need for investigating the precise mechanisms underlying the relationship between Fe and FGF23 to optimize the clinical management of anemia, particularly in the context of renal dysfunction.
Type of Medium:
Online Resource
ISSN:
0931-0509
,
1460-2385
DOI:
10.1093/ndt/gfad063c_5517
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
1465709-0
