Raymond Pratt

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

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.

Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients

Background Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Methods Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. Results In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2–0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (−0.9 pg versus −0.4 pg, P < 0.001) and serum ferritin (−133.1 µg/L versus −69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. Conclusions FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.

Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers

Ferric pyrophosphate citrate (Triferic) is a water‐soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double‐blind, randomized, placebo‐controlled, single‐, ascending‐dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron‐replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFetot), transferrin‐bound iron (TBI), hepcidin‐25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFetot was observed in placebo‐treated subjects. Concentrations of sFetot and TBI increased rapidly after drug administration, with maximum serum concentrations (Cmax) reached at the end of infusion. Increases in baseline‐corrected Cmax and area under the concentration‐time curve from 0 to the time of the last quantifiable concentration (AUC0‐t) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half‐life 1.2‐2 hours). No significant changes from baseline in serum hepcidin‐25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation.

Ferric Pyrophosphate Citrate (Triferic), a novel therapy that treats anemia of inflammation and overcomes functional iron deficiency

The highly-dosed infusion with Procaine-HCl with sodium-bicarbonate as additive was firstly published twenty years ago. The method advanced to a routine in many centers for pain treatment, rehabilitation and natural medicine. The aim of the procedure is the systemic use of the various pharmacological features of Procaine, especially to inhibit pain and inflammation, for vasodilatation, anti-oxidation and to harmonize the vegetative nervous system. On one hand shall the addition of sodium-bicarbonate balance the common latent pH-decrease in the periphery. On the other hand also the degradation products of Procaine (DAE and PABA) have a systemic effect. For the safety of the patients and to improve the success rate of the method it was shown that the classic Procaine-Base-infusion should be only realized on the base of a prior acid-base-diagnostic. Review Article Citation: Ralf Oettmeier, Uwe Reuter. The Procaine-Base-Infusion: A Review after Twenty Years of Use. J Med Clin Res & Rev. 2017;F Pyrophosphate Citrate (FPC) is a novel, highly soluble iron salt for parenteral delivery via hemodialysis solution. FPC donates iron directly and rapidly to transferrin, avoiding iron sequestration in the reticuloendothelial system. Randomized, placebo-controlled clinical trials in chronic hemodialysis (CKD 5HD) patients have demonstrated that FPC delivery by hemodialysis can maintain iron balance by replacing regular iron losses, while reducing ESA use and maintaining hemoglobin (Hgb). In the double-blind PRIME study, 104 iron replete (serum ferritin, 20Background: Kidney transplant has been developing rapidly in Indonesia in recent years. Cipto Mangunkusumo General Hospital (CMGH) has performed 491 transplants in the last 6 years. The survival of graft and patient in CMGH in the first year was 95.4% and 88.5%. However, there was no data on survival in the next following years. This study was aimed to establish the 3-year survival of graft and patient of kidney transplant in CMGH. Methods and findings: Descriptive study with retrospective cohort design on all kidney transplant patients at CMGH from January 2011 to May 2014. Each patient was observed from the date of transplantation until death or May 2017. Graft and patient survival rate within 3 years and at the end of the study were documented. The Kaplan-Meier method was used to describe graft and patient survival. 138 of 147 kidney transplant recipients were included. All patients receive kidneys from living donors. The mean age was 47.94 + 14.06 years old. The 3-year death-censored graft survival, all-cause graft survival and patient survival were 90.6%, 76.1% and 79.7%, in sequence. At the end of the study, these survival rates were lower (89.1%, 71.7%, and 76.1%). The median of observation time was 42 months (36-72 months). Kaplan-Meiers curve showed the highest mortality rates occurred in the early months. Infection was the main cause of death. Conclusion: The 3-year graft and patient survival in CMGH 90.6% and 79.7%. Infection is the major factor that affects the survival rates.