Skip to content
Keywords: renal failure, chronic renal failure, anemia, iron supplement, low iron, iron, liposome
MULTICENTER RANDOMIZED STUDY WITH AN IRON NUTRACEUTICAL DELIVERED VIA LIPOSOMES IN PATIENTS WITH ANEMIA CAUSED BY CHRONIC KIDNEY DEFICIENCY
RANDOMIZED MULTICENTER STUDY ON A SUPPLEMENT OF IRON PYROPHOSPHATE CONTAINED IN LYPOSOMES IN PATIENTS WITH ANEMIA CAUSED BY CHRONIC KIDNEY DEFICIENCY
Giovanni Di Fiore, Carmelo Adriano Piluso and Francesco Ravaglia
Introduction: anemia of chronic renal failure
One of the side effects of chronic renal failure (CRI) isanemia, which is associated with worsening quality of life and also increased mortality from other cardiovascular diseases.
The cause of anemia in patients with CRI is reduced Erythropoietin (EPO) production in the kidney, and as a result of this, there is also reduced red blood cell production, since erythropoietin is the main hormone that regulates its production. However, low iron availability, or its deficiency, also plays a key role in the development of CRI anemias: in this case, erythrocyte production is limited by the amount of iron available, which may be low due to reduced systemic iron supply or, and more commonly in patients with this condition, due to reduced absorption.
In patients with CDI, situations of chronic inflammation often exist at the same time and, as known in the literature, such situations are associated with a condition of “chronic disease anemia,” in which dietary iron absorption is limited and its presence in the body is concentrated mainly in the reticuloendothelial system rather than in the bloodstream. It is also known that the condition of anemia of chronic disease can cause a state of reduced sensitivity to erythropoiesis-promoting substances, making it even more difficult to treat the condition.
How has renal failure been treated to date?
For the past 30 years, the cornerstones of therapy for CRI have been treatment with EPO, or its synthetic derivatives, and dietary supplementation through the use of iron(II) sulfate supplements or intravenously using formulations containing ferric carboxymaltose. However, both supplementation methods have quite a few side effects. In addition, the modus operandi for the treatment of CRI has recently changed with a primary focus on stabilizing the blood iron level, then followed by hematopoiesis-promoting treatment: there is, therefore, a focus on iron supplementation. As mentioned, however, existing iron supplements present quite a few problems because intravenous application can cause further renal damage, accelerate infection by pathogenic bacteria, aggravate atherosclerosis by generating oxidative stress, and finally cause endothelial damage and anaphylaxis.
In light of these problems with intravenous intake, theEMA (European Medicine Agency) has ruled that this method for iron supplementation is only feasible when the route of oral supplements has already been tried with negative results. As for oral iron supplements using formulation with FeSO4, the latter have poor absorption in the intestine and generate problems such as nausea, vomiting, heartburn, loss of appetite, diarrhea, and all these side effects make it difficult to use them to improve blood iron levels and thus worsen the patient’s therapeutic adherence, thwarting therapy.
What are the latest therapeutic frontiers?
In recent years, alternative methodologies of formulating iron supplements to be taken orally have been developed that use liposome-carried iron instead of the usual saline form.
This form of the active ingredient has greater bioavailability in the intestine by virtue of its chemical formulation, as it consists of an aqueous solution of Ferro pyrophosphate surrounded by a vesicle of phospholipids: the liposome. This allows such vesicles to easily enter the interior of intestinal villus cells and promote significantly greater absorption of the iron solution contained therein than equal intestinal concentrations of Iron sulfate. In addition, no side effects from liposome intake have been reported so far in the literature, and it is therefore reasonable to assume that, under strict medical supervision to avoid excessive iron intakes, liposomal iron is an effective answer to the problem of anemia in patients with CRI and forced on dialysis.
Objective of the study
The study aims to evaluate the efficacy of iron supplementation with a microencapsulated pyrophosphate iron supplement (micellar iron), FERTOP30cpr®, using blood values of hemoglobin, hematocrit, free iron and ferritin as reference at the start of therapy and after 3 months of treatment. At the same time, the sustainability for prolonged treatment is also assessed, noting any side effects.
Materials and methods
Forty-four dialysis patients with chronic renal failure, aged 20 to 96 years, both male and female, were recruited for the study. Female patients of childbearing age were asked whether they were pregnant. In addition, all patients were asked if they were from previous treatment with Iron supplements before starting the study, and if so, which supplements they were taking. It was asked if they were currently being treated with EPO or similar medications. The researcher, taking the patient’s blood tests at the beginning of therapy, noted their Hemoglobin, Hematocrit %, mean cell volume of red blood cells, Blood Iron and Ferritin values: based on these initial values, he determined the dosage of taking the supplement.
In fact, the posology of the treatment was as follows:
Patients with severe hemoglobin hemoglobin deficiency, (<11 g/dL) were advised to take 2 tablets of Fertop daily, one during lunch and one during dinner, for the first month, followed by taking 1 tablet daily after the first month and until study completion.
For patients with mild hemoglobin deficiency(11-14 g/dL in men, 11-12 g/L in women), only 1 tablet per day taken during lunch was recommended until study completion.
After 3 months of treatment, new blood tests were performed to reevaluate the same values and quantify any improvements in these parameters.
Criteria for inclusion and exclusion
- Dialysis patients with chronic renal failure who have anemia from chronic disease
Excluded from the study are:
- Patients already being treated with other iron supplements, either oral or intravenous.
Features of FERTOP 30CPR
Fertop 30 Cpr contains:
Microencapsulated pyrophosphate iron: As previously mentioned, micellar iron represents a more bioavailable form and has fewer side effects than iron sulfate and carboxymaltose iron.
Folic Acid: Involved in hematopoietic process and cell division, it assists erythrocyte production.
Vitamin C: Promotes iron absorption and exerts antioxidant action.
Results of the study on the treatment of anemia in patients with CRI
Forty-four patients participated in the study, including 19 men and 25 women; of the 25 women who participated, one was pregnant. The mean age of the patients was found to be 66.77 years. Of these 44 patients 12, or 27.27%, were from failed therapies with other iron supplements. The patients were found to have a mean hemoglobin value of 10.80 g/dL at the beginning of the study, which was indicative of severe deficiency, a hematocrit value of 34.17% sideremia of 67.29 μg/dL and a ferritinemia value of 41.34 μg/L.
These mean values were below normal minima for hemoglobin and hematocrit, but within acceptable, though low, ranges for sideremia and ferritinemia. Following the 3-month supplement treatment, the values found were: 12.60 g/dL for hemoglobin, 40.40% for hematocrit, 76.75 μg/dL for blood iron, and 114.59 μg/l for ferritin. These values denote a marked improvement, amounting to 14.35 percent on hemoglobin, 15.40 percent on hematocrit, 12.33 percent on blood iron, and 63.92 percent on ferritin. The values reported at the end of the study were found to be improved for all patients in the study.
In addition, no patients presented side effects, and most patients reported being satisfied with the therapy and feeling stronger.
Conclusions of the study
Fertop did not cause any major side effects in these patients and improved the condition objectively, as shown by analysis at the end of treatment. It proves to be an excellent option for the management of sideropenic patients on dialysis treatment and with chronic renal failure.
Would you like to find out more about FERTOP 30CPR?
Bibliographical references
[1] Folkert, V. W., Michael, B., Agarwal, R., Coyne, D. W., Dahl, N., Myirski, P., … & Ferrlecit® Publication Committee. (2003). Chronic use of sodium ferric gluconate complex in hemodialysis patients: safety of higher-dose (≥ 250 mg) administration. American journal of kidney diseases, 41(3), 651-657.
[2] KDOQI; National Kidney Foundation; II. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis 2006; 47: S16-S85
[3] Keating, G. M. (2015). Ferric carboxymaltose: a review of its use in iron deficiency. Drugs, 75, 101-127.
[4] Maladkar, M., Sankar, S., & Yadav, A. (2020). A novel approach for iron deficiency anaemia with liposomal iron: concept to clinic. Journal of Biosciences and Medicines, 8(09), 27.
[5] Nissenson, A. R., & Charytan, C. (2003). Controversies in iron management: Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease. Kidney International, 64, S64-S71.
[6] Perazella, M. A., Brewster, U. C., & Perazella, M. A. (2004, January). Intravenous iron and the risk of infection in end-stage renal disease patients. In Seminars in dialysis (Vol. 17, No. 1, pp. 57-60). Oxford, UK: Blackwell Science Inc.
[7] Pisani, A., Riccio, E., Sabbatini, M., Andreucci, M., Del Rio, A., & Visciano, B. (2015). Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrology dialysis transplantation, 30(4), 645-652.
[8] Wysowski, D. K., Swartz, L., Vicky Borders-Hemphill, B., Goulding, M. R., & Dormitzer, C. (2010). Use of parenteral iron products and serious anaphylactic-type reactions. American journal of hematology, 85(9), 650-654.
