Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post-hoc analysis of a prospective study

Abstract

BackgroundSome parenteral iron therapies have been found to be associated with hypophosphatemia. The mechanism of the decrease in serum phosphate is unknown. The aim of this study is to examine the effect of IV ferric carboxymaltose(FCM) on phosphate metabolism and FGF23 levels in patients with chronic kidney disease(CKD).MethodsThis is a post-hoc analysis of a prospective study carried out in 47 non-dialysis CKD patients with iron-deficiency anaemia who received a single 1000 mg injection of FCM. Markers of mineral metabolism (calcium, phosphate, 1,25-dihydroxyvitamin D, PTH and FGF23[c-terminal]) were measured prior to FCM administration and at week 3 and week 12 after FCM administration. Based on the measured levels of serum phosphate at week 3, patiens were classified as hypophosphatemic or non-hypophosphatemic.ResultsSerum phosphate levels decreased significantly three weeks after FCM administration and remained at lower levels at week 12 (4.24 ± 0.84 vs 3.69 ± 1.10 vs 3.83 ± 0.68 mg/dL, respectively, p < 0.0001. Serum calcium, PTH and 1,25-dihydroxyvitamin D did not change over the course of the study. Serum FGF23 decreased significantly from 442(44.9-4079.2) at baseline to 340(68.5-2603.3) at week 3 and 191.6(51.3-2465.9) RU/mL at week 12, p < 0.0001. Twelve patients were non-hypophosphatemic and 35 hypophosphatemic. FGF23 levels decreased in both groups, whereas no changes were documented in any of the other mineral parameters.ConclusionsIn non-dialysis CKD patients, FCM induces reduction in serum phosphate levels that persists for three months. FCM causes a significant decrease in FGF23 levels without changes to other bone metabolism parameters.

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

“…However, the study of Prats et al was longer and the changes in serum phosphate persisted for 3 months [15]. That study showed, among others, that a single high dose of IV iron (1000 mg) may lead to significant changes of FGF23 and serum phosphate.…”

“…In another study the use of ferric carboxymaltose, in non-dialysis patients, Prats et al showed a reduction of serum phosphate levels that persisted for up to 3 months after iron infusion and it was associated with a decrease of serum FGF23 but there were no changes of other bone metabolism parameters [15]. These results are consistent with ours at least in the short-term, since we did not observe any significant changes of plasma BAP, PTH or serum calcium concentration.…”

“…Additionally, several recent studies have shown that the intravenous iron supplementation can lead to potentially unfavourable changes of mineral metabolism both in healthy humans and in CKD patients [15, 16]. Moreover, the latter group is characterized by the presence of subclinical chronic inflammation.…”

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

“…After oral or intravenous iron, various FGF23 responses were registered depending on the iron type and the population [21,22]. The decrease of phosphate after iron in the HD population is probably the result of the PTH decrease, and contrary to the healthy population, no iFGF23 increase was detected [23][24][25]. Whatever the iron form used and the population considered, iron administration decreases cFGF23 by decreasing the transcription of the gene.…”

Hipofosfatemia asociada a la administración intravenosa de hierro carboximaltosa en pacientes con anemia ferropénica. Un efecto secundario frecuente

“…La duració n de la HF en el presente estudio presenta mayor incertidumbre debido a la falta de datos en algunos pacientes pero, asumiendo la ausencia de HF en los pacientes en los que no se determinó el fosfato sé rico, la incidencia real de HF se situaría al menos en el 20% para el P22-35 y en el 6% para el P60-180. Prats et al 7 han encontrado que los pacientes que desarrollan HF mantienen concentraciones por debajo de la basal a las 12 sem de la infusió n de HCMiv.…”