pyrophosphate and Anemia

Treatment of anemia remains an integral component in the care of patients with end stage kidney disease receiving dialysis. Currently, both erythropoiesis stimulating agents and iron replacement agents remain important anemia management strategies for patients undergoing hemodialysis (HD). Ferric pyrophosphate citrate (FPC) was approved by the U.S. Food and Drug Administration in January 2015 as an iron replacement product in adult patients receiving long-term maintenance HD. FPC is administered to patients on HD through the dialysate. Multicenter randomized, placebo-controlled phase three clinical studies (CRUISE 1 and 2) have found dialysate FPC to maintain hemoglobin level and iron balance in patients receiving chronic HD. Adverse events were similar in both the dialysate FPC-treated and placebo groups. Another study showed a significant reduction in the prescribed erythropoietin-stimulating agents dose at the end of treatment in the dialysate FPC-treated group compared with placebo. These studies have shown that dialysate FPC is efficacious and well tolerated. In this article, we review clinical studies evaluating the efficacy and safety of FPC and also propose a protocol for iron replacement in HD units where dialysate FPC is to be used.

Topics: Anemia; Clinical Trials as Topic; Diphosphates; Hematinics; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

Topics: Anemia; Diphosphates; Female; Humans; Menopause; Organophosphonates; Osteoclasts; Osteoporosis; Time Factors

It is challenging to find an iron compound that combines good bioavailability with minimal sensory changes when added to seasonings or condiments. Ferric pyrophosphate (FePP) is currently used to fortify bouillon cubes, but its bioavailability is generally low. Previously, the addition of a stabilizer, sodium pyrophosphate (NaPP), improved iron bioavailability from a bouillon drink.. We assessed whether there is a dose-response effect of added NaPP on iron bioavailability from local meals prepared with intrinsically labeled FePP-fortified bouillon cubes in young Nigerian women using iron stable isotope techniques.. In a double-blind, randomized, cross-over trial, women (n = 24; aged 18-40 y; mean BMI 20.5 kg/m2) consumed a Nigerian breakfast and lunch for 5 d prepared with bouillon cubes containing 2.5 mg 57Fe (as FePP) and 3 different molar ratios of NaPP: 57Fe (0:1, 3:1, and 6:1). Iron bioavailability was assessed by measuring 57Fe incorporation into erythrocytes 16 d after each 5 d NaPP: 57Fe feeding period. Data were analyzed using a linear regression model of log iron absorption on NaPP ratio, with body weight and baseline body iron stores as covariates and subject as a random intercept.. Of the women included, 46% were anemic and 26% were iron deficient. Iron bioavailability was 10.8, 9.8, and 11.0% for the 0:1, 3:1, and 6:1 NaPP:57Fe treatments, respectively. There was no dose-response effect of an increasing NaPP:57Fe ratio (β ± SE: 0.003 ± 0.028, P = 0.45).. In this study, the addition of NaPP did not increase iron bioavailability from FePP-fortified bouillon cubes. However, iron bioavailability from the Nigerian meals prepared with FePP-fortified bouillon cubes was higher than expected. These results are encouraging for the potential of bouillon cubes as a fortification vehicle. Further studies are needed to assess the effect of FePP-fortified bouillon cubes on improving iron status in low-income populations. This trial was registered at clinicaltrials.gov as NCT02815449.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; Biological Availability; Cross-Over Studies; Diphosphates; Double-Blind Method; Erythrocytes; Female; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron Isotopes; Meals; Nigeria; Young Adult

Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children.. A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4).. After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 μg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001).. IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions.. http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Topics: Amodiaquine; Anemia; Antimalarials; Child, Preschool; Cote d'Ivoire; Diphosphates; Drug Combinations; Edetic Acid; Ferric Compounds; Food, Fortified; Hemoglobins; Humans; Infant; Inflammation; Iron; Iron Deficiencies; Malaria; Male; Prevalence; Pyrimethamine; Sulfadoxine

To evaluate the role of recombinant human erythropoietin in reducing the need for homologous blood transfusion during operations by studying its effect on the recovery of postoperative anaemia.. Randomised controlled trial.. University hospital, Japan.. 10 patients with gastric cancer undergoing distal gastrectomy.. 5 Patients were given erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day intravenously for seven days before operation and 14 days afterwards, and 5 were given ferric pyrophosphate 40 mg/day alone (control group).. Packed cell volume, haemoglobin concentration, and white and red cell counts.. There was no significant change in packed cell volume after the operation in the erythropoietin group, but in the control group it dropped from a mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05). Haemoglobin concentrations were significantly higher in the erythropoietin group than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p < 0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation.. Erythropoietin prevented postoperative anaemia after gastrectomy as judged by packed cell volume, haemoglobin concentration, and red cell count. Erythropoietin given before and after operation therefore has the potential to reduce the need for homologous blood transfusion during and after major operations.

Topics: Adult; Aged; Anemia; Blood Cell Count; Diphosphates; Erythropoietin; Female; Gastrectomy; Hematocrit; Hemoglobins; Humans; Iron; Male; Middle Aged; Pilot Projects; Postoperative Care; Postoperative Complications; Preoperative Care; Recombinant Proteins; Stomach Neoplasms; Time Factors

Anemia is a common complication in patients with hemodialysis-dependent chronic kidney disease (HDD-CKD). Anemia is principally the result of erythropoietin deficiency, inflammation, and iron deficiency. High molecular weight iron oxide nanoparticles (IONP) are routinely administered intravenously to replace iron losses and, although effective, there are lingering concerns about possible safety issues. Ferric pyrophosphate citrate (FPC, Triferic, Triferic AVNU [Triferic and Triferic AVNU are the proprietary name for ferric pyrophosphate citrate. Triferic and Triferic AVNU are registered trademarks of Rockwell medical Inc.]) is a complex iron salt that donates iron directly to plasma transferrin. FPC is devoid of any carbohydrate moiety and is administered

Topics: Anemia; Anemia, Iron-Deficiency; Citrates; Dialysis Solutions; Diphosphates; Ferric Compounds; Hemoglobins; Humans; Inflammation; Iron; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome