SaO029CHRONIC KIDNEY DISEASE MODIFIES DEVELPMENT OF HYPOPHOSPHATEMIA AFTER FERRIC CARBOXYMALTOSE INFUSION

Abstract

Introduction and Aims: Iron deficiency is a frequent co-morbidity in in patients with heart failure with reduced ejection fraction (HFrEF). Current research has shown that intravenous iron replenishment increases exercise tolerance and quality of life in HFrEF patients with iron deficiency. However, case reports have linked the administration of FCM to the development of hypophosphataemia and osteomalacia with fractures. Since Fibroblast Growth Factor 23 (FGF23) is a key regulator of phosphate and Vitamin D metabolism we sought to determine if the administration of FCM increases levels of circulating FGF23 and how this associates with hypophosphatemia induction. Method(s): In this pilot study a total of 23 stable HFrEF patients with a left ventricular ejection fraction < 40% (12 with chronic kidney disease (CKD) as defined by GFR <60ml/min/1.73m2 (Group HFrEF(+)CKD) and 11 with GFR > 60 ml/min, Group HFrEF) were identified with iron deficiency (Ferritin < 100mg/dl or Ferritin 100-300 mg/dl if TSAT <20%) and received a single dose of 1000 mg FCM. Blood was drawn before, immediately post administration as well as on days 1, 7,14 and 28. Levels of intact (iFGF23) and c-terminal (cFGF23) FGF23 were determined alongside serum levels of phosphate and 1,25 Vitamin D (calcitriol). Result(s): Baseline serum phosphate, iFGF23, c-termFGF23, fractional urinary excretion excretion of phosphate were higher in HFrEF(+)CKD pts compared to HFrEF patients. Administration of FCM resulted in a concordant increase in Ferritin (maximum day 7) and TSAT (maximum immediately post-infusion) in both groups. After administration of FCM, iFGF23 levels rose in both groups reaching their peak already at Day 1 (HfREf(+)CKD from baseline 214,26 188,6 To 384,6 6 91,3 pg/ml (factor 1.8); Group HFrEF from baseline 17,28611.2to 187,5 6 42,9 pg/ml (Factor 11)). In patients without CKD iFGF23 remained significantly elevated until day 28. In contrast, c-term FGF23 levels decreased towards day 28 in both groups. Serum phosphate decreased significantly only in HFrEF patients without CKD and reached their nadir at Day 14 (-0,34mmol/l compared to baseline) and remained significantly decreased at day 28. Hypophospatemia as defined below 0.8 mmol/L developed in 14 out of 23 pts. Levels of 1,25-Vitamin D significantly decreased in both groups by over 50% with a similar time course as serum phosphate (i.e. partial recovery until day 28 post-infusion). Conclusion(s): We show for the first time in a prospective study that the correction of iron deficiency in patients with HFrEF with FCM increases significantly intact FGF23 levels while decreasing c-term FGF23-thus pointing towards impairement of its degradation. These findings were particularly strong in HFrEF patients without concomitant CKD. The physiological response to increased iFGF23 was clearly detectable: reduction of serum phosphate and increased urinary phosphate excretion. Our study underlines the need to assess long-term safety of FCM administration in HFrEF patients since the observed derangements in FGF23-phosphate metabolism might impair myocardial function and induce osteomalacia particurlay with repetitive dosing.