Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients

Abstract

Ferric pyrophosphate citrate (FPC) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin. The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent (ESA) use and maintain hemoglobin in hemodialysis patients. This 9-month, randomized, placebo-controlled, double-blind, multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly. The FPC group received dialysate containing 2 μmol/l of iron. The placebo group received standard dialysate. A blinded central anemia management group facilitated ESA dose adjustments. Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l. The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment. Secondary end points included intravenous iron use and safety. At the end of treatment, there was a significant 35% reduction in prescribed ESA dose in FPC-treated patients compared with placebo. The FPC patients used 51% less intravenous iron than placebo. Adverse and serious adverse events were similar in both groups. Thus, FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients.

New Options for Iron Supplementation in Maintenance Hemodialysis Patients

“…In that study, patients treated with ferric pyrophosphate citrate by dialysate for 6 months were noted to have a decrease in IV iron requirements to maintain iron balance compared to the control group (6 vs 10 mg/wk, respectively; P 5 0.001). Since that time, 2 large randomized controlled trials comparing this iron salt to placebo have been conducted, 83,84 and the product was approved by the US Food and Drug Administration (FDA) in 2015. At a dialysate iron concentration of 2 mmol/L (110 mg/L), ferric pyrophosphate citrate provides 5 to 7 mg of iron to the patient during each dialysis session, equivalent to the estimated amount of iron lost during a dialysis treatment.…”

“…83 IV iron administration during the randomization period was based on TSAT and serum ferritin values, and prescribed ESA dose was based on hemoglobin levels and the rate of change. At the conclusion of the study, mean hemoglobin levels were not statistically different between the 2 groups, but there was a 48% lower IV requirement (P 5 0.044) and 35% lower ESA requirement (P 5 0.045) among patients treated with the iron salt-containing dialysate.…”

Characterization of an Animal Model to Study Risk Factors and New Therapies for the Cardiorenal Syndrome, a Major Health Issue in Our Aging Population

“…An alternative approach could be to directly interfere with the calcification process by for example treatment with the endogenic calcification inhibitor pyrophosphate either or not in combination with its most important degrading enzyme tissue nonspecific alkaline phosphatase. Another therapeutic strategy could consist in the therapeutic use of ferric pyrophosphate (Fe-PPi or Triferic) [27] which would allow us to directly evaluate the combined effect of this treatment on vascular calcification and iron-deficiency-related anemia in one and the same animal. As such, our current model again would enable to test the effects of these particular treatments on all aspects of the CRS.…”

Iatrogenic iron overload and its potential consequences in patients on hemodialysis

“…HIF, a key regulatory protein which stimulates erythropoietin and transferrin production, reduces hepcidin production, and thereby modulates iron absorption and metabolism, although the direct or indirect influence (via erythropoietin) of HIF on hepcidin modulation is still an open question [89]. In addition to HIF stabilizers, iron administration via the dialysate ferric pyrophosphate citrate (Triferic ® ) and a ferric citrate-based phosphate binder (Auryxia ® ) are new therapeutic options for compensating iron deficiency related to blood loss in hemodialysis patients and for providing the iron required for erythropoiesis [90][91][92][93]. Ferric pyrophosphate citrate (Triferic ® ) rapidly delivers iron directly and safely to the bone marrow (5-7 mg iron) during hemodialysis sessions via the dialysate, efficiently matching the amount of iron required by ESA to generate red blood cells, without increasing ferritin levels [90].…”

“…In addition to HIF stabilizers, iron administration via the dialysate ferric pyrophosphate citrate (Triferic ® ) and a ferric citrate-based phosphate binder (Auryxia ® ) are new therapeutic options for compensating iron deficiency related to blood loss in hemodialysis patients and for providing the iron required for erythropoiesis [90][91][92][93]. Ferric pyrophosphate citrate (Triferic ® ) rapidly delivers iron directly and safely to the bone marrow (5-7 mg iron) during hemodialysis sessions via the dialysate, efficiently matching the amount of iron required by ESA to generate red blood cells, without increasing ferritin levels [90]. The new phosphate binder composed of ferric citrate (Auryxia ® ), besides its ability to chelate intestinal phosphate, reduces the need for IV iron in dialysis patients, thus theoretically lowering the risk of iatrogenic iron overload and re-establishing oral iron as an efficient iron source; alternatively it may cause intestinal side effects precluding its ability to reduce IV iron dose [91][92][93].…”