High Dose Intravenous Iron, Mineral Homeostasis and Intact FGF23 in Normal and Uremic Rats

Background: High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased mortality in the chronic kidney disease (CKD) population. CKD patients are often treated with iv iron therapy in order to maintain iron stores and erythropoietin responsiveness, also in the case of not being iron depleted. Therefore, the effect of a single high iv dose of two different iron preparations, iron isomaltoside 1000 (IIM) and ferric carboxymaltose (FCM), on plasma levels of FGF23 and phosphate was examined in normal and uremic iron repleted rats.

Methods: Iron was administered iv as a single high dose of 80 mg/kg bodyweight and the effects on plasma levels of iFGF23, phosphate, Ca2+, PTH, transferrin, ferritin and iron were examined in short and long term experiments (n = 99). Blood samples were obtained at time 0, 30, 60, 180 minutes, 24 and 48 hours and in a separate study after 1 week. Uremia was induced by 5/6-nephrectomy.

Results: Nephrectomized rats had significant uremia, hyperparathyroidism and elevated FGF23. Iron administration resulted in significant increases in plasma ferritin levels. No significant differences were seen in plasma levels of iFGF23, phosphate and PTH between the experimental groups at any time point within 48 hours or at 1 week after infusion of the iron compounds compared to vehicle.

Conclusions: In non-iron depleted normal and uremic rats a single high dose of either of two intravenous iron preparations, iron isomaltoside 1000, and ferric carboxymaltose, had no effect on plasma levels of iFGF23 and phosphate for up to seven days.