Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5

Abstract

Background/Aims: Both iron deficiency and chronic inflammation are highly prevalent in patients with chronic kidney disease (CKD). The effect of intravenous iron infusion on mineral metabolism in CKD may be modified by inflammation. Intravenous iron theraphy may reduce peripheral degradation, secretion, clearence of iFGF23 and lead to hypophosphatemia. The aim of the study was to evaluate the effect of intravenous iron on mineral metabolism in CKD patients. Methods: 35 non-dialysis patients with CKD stages 3-5. received 100 mg/24h of ferric oxide saccharated solution for 5 days. Serum calcium (Ca), phosphorus (P), parathormone (PTH), intact-FGF23 (iFGF23), C-terminal-FGF23 (cFGF23), bone alkaline phosphatase (BAP) and high-sensitive CRP were assessed on day 1 and 3 at baseline and 2 hours after each dose administration and once on day 6. Plasma iFGF23 and cFGF23, as well as serum BAP were measured with ELISA and other parameters with standard automated laboratory methods. Results: Serum iFGF23 increased after iv iron on day 1 and 6 (from 268.9±446.5 to 326.3±529.9 on day 1; p=0.05 and to 451.4±601 pg/mL on day 6; p=0.03). cFGF23 was reduced only on day 1 (from 654.3±441.3 to 473.6±414 RU/mL; p=0.016). P concentration decreased significantly two hours after the first iron infusion (from 1.69±0.5 to 1.54±0.35 mmol/l; p=0.003). In following days the changes of cFGF23, P and of other calcium-phosphate metabolism were not significant. Serum CRP correlated neither with iFGF-23 nor cFGF-23. Conclusion: Intravenous iron supplementation may only transiently affect the production and degradation of FGF23 resulting in hypophosphatemia at the commencement of iron therapy. Chronic low-grade inflammation does not seem to play a role in that mechanism.

Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia

“…Serum C-FGF23 levels were significantly lower compared to the healthy controls. This is in line with previous studies investigating the changes in C-FGF23 following the iv administration of Fe [19,20,33]. iFGF23 found to be higher in Th patients -although not statistically significant (p = 0.14), implying a decreased iFGF23 cleavage.…”

A Pooled Analysis of Serum Phosphate Measurements and Potential Hypophosphataemia Events in 45 Interventional Trials with Ferric Carboxymaltose

“…Hypophosphataemia is a known adverse drug reaction with ferric carboxymaltose (FCM) listed in the Ferinject ® (FCM) Prescribing Information since registration of the product [17], and it is often transient and, in most cases, asymptomatic. A decrease in serum PO 4 3− has also been reported with several other IV iron preparations [18][19][20]. However, the potential clinical relevance of a decrease in serum PO 4 3− has been challenging to establish due to the generalised symptoms of HP.…”

Crosstalk between fibroblast growth factor 23, iron, erythropoietin, and inflammation in kidney disease

“…Hypophosphatemia occurred in 50.8% of the ferric carboxymaltose group, with 10% of patients having severe hypophosphatemia and 30% having persistent hypophosphatemia 4 weeks after the last dose, compared with 0.9% of the ferumoxytol group (44)**. Iron-induced hypophosphatemia was previously reported in case reports dating back to 1982 as well as smaller retrospective and pilot studies, in some cases associated with serious musculoskeletal complications (46)(47)(48)(49)(50)(51). These complications have been observed with only a subset of IV iron preparations, mainly ferric carboxymaltose, iron polymaltose, and saccharated iron oxide, suggesting it is not a class effect of all IV iron, but may be a consequence of the carbohydrate shell associated with certain preparations [(44)**, (46), (48)].…”