Ponad 7000 publikacji medycznych!
Statystyki za 2021 rok:
odsłony: 8 805 378
Artykuły w Czytelni Medycznej o SARS-CoV-2/Covid-19

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu tutaj
© Borgis - Postępy Nauk Medycznych 10/2015, s. 693-697
Katarzyna Chmiel-Majewska, Dorota Daniewska, Tomasz Żelek, *Ryszard Gellert
Stymulacja za pomocą izomaltozydu 1000 żelaza (III) erytropoezy zahamowanej przez niedobór żelaza u hemodializowanych pacjentów z niedokrwistością nie prowadzi do nadmiernego wysycenia transferyny – badanie retrospektywne
Stimulation of iron-restricted erythropoiesis with iron (III) isomaltoside 1000 does not oversaturate transferrin in haemodialysed patients with anaemia – a retrospective study
Department of Nephrology and Internal Medicine, Center of Postgraduate Medical Education, P. Jerzy Popiełuszko Bielański Hospital, Warszawa
Head of Department: prof. Ryszard Gellert, MD, PhD
Wstęp. Niedobór żelaza, zarówno względny, jak i bezwzględny, przyczynia się do rozwoju niedokrwistości w przebiegu schyłkowej niewydolności nerek. Dożylna suplementacja żelaza jest standardowym postępowaniem u pacjentów hemodializowanych. Dożylne preparaty żelaza różnią się pod względem toksyczności, w zależności od tego, ile wolnego jonu żelaza, wykazującego szkodliwy wpływ na tkanki, przedostaje się do osocza. Wolne jony żelaza przechwytywane są przez apotransferynę osocza zanim uszkodzą tkanki, czego miarą jest wzrost TSAT.
Cel pracy. Celem badania była ocena u pacjentów dializowanych zmian wysycenia transferyny po dożylnej suplementacji izomaltozydu 1000 żelaza (III).
Materiał i metody. Miarą zmian stężenia apotransferyny były różnice TSAT. Badanie przeprowadzono w dwóch ośmioosobowych grupach pacjentów hemodializowanych z powodu schyłkowej niewydolności nerek z wyjściowym TSAT < 35%. W pierwszej grupie podawano żelazo w dwóch dawkach po 100 mg w odstępie tygodniowym. W drugiej grupie pierwsza dawka izomaltozydu wynosiła 200 mg, druga 100 mg. Zmiany TSAT obserwowano 210 minut po podaży dożylnej izomaltozydu żelaza (III). Wyniki poddano analizie statystycznej z użyciem pakietu STATISTICA.
Wyniki. Izomaltozyd 1000 żelaza (III) zarówno w dawce 100, jak i 200 mg powodował znamienny statystycznie, przejściowy wzrost TSAT. Po dawce 200 mg wartości TSAT były znamiennie wyższe w porównaniu z dawką 100 mg (p = 0,026264). W żadnym przypadku nie zaobserwowano jednak TSAT przekraczającego 60%. Nie stwierdzono też żadnych działań niepożądanych leku.
Wnioski. U pacjentów hemodializowanych dawki 100 i 200 mg izomaltozydu 1000 żelaza (III) powodują umiarkowany, przejściowy wzrost wartości TSAT. Dawka 200 mg wydaje się bezpieczna tylko przy znacznym niedoborze żelaza.
Introduction. Iron deficiency, either absolute or relative, contributes to the development of anaemia in end-stage renal failure. Intravenous iron supplementation is a standard treatment in patients on haemodialysis therapy. Available intravenous iron preparations differ in toxicity, dependent on the amount of potentially harmful free iron that is detached from the transporting particle. Interception of free iron by apotransferrin results in TSAT increase.
Aim. The aim of this study was to assess the changes in TSAT after injection of iron (III) isomaltoside 1000 in haemodialysis patients.
Material and methods. The study was conducted in two groups of anemic patients on maintenance haemodialysis for end-stage renal failure. Each group comprised 8 patients with baseline TSAT < 35%. Two weekly doses of 100 mg iron (III) isomaltoside 1000 were administered in the first group. In the second group, 200 mg iron (III) isomaltoside 1000 was administered as the first weekly dose, followed by a 100 mg dose. The changes in TSAT were measured 210 minutes after each administration. The results were analysed with the STATISTICA software.
Results. Both 100 and 200 mg of iron (III) isomaltoside 1000 caused statistically significant, transient increase in TSAT values. TSAT values after 200 mg isomaltoside were significantly higher in comparison to 100 mg (p = 0.026264). In neither case the TSAT values reached 60%. No adverse effects of supplementation were observed.
Conclusions. In haemodialysis patients iron (III) isomaltoside 1000 causes moderate and transient increase in TSAT values. The 200 mg iron (III) isomaltoside 1000 seems safe only in patients with significant iron depletion.
Erythropoiesis is an intricate, multistage process of differentiation of early pluripotent erythroid progenitors to mature enucleated erythrocytes. The process is dependent on numerous exogenous and endogenous factors, such as iron homeostasis, hypoxia, stress, growth and transcription factors (1). As erythropoietin is one of the strongest molecules stimulating erythropoiesis, its low production in diseased renal tissue may explain why anaemia is a prevalent complication of chronic kidney disease (CKD). However, iron deficiency-limited erythropoiesis is a compelling problem, contributing to the development of anaemia in chronic kidney disease and limiting efficacy of treatment with erythropoiesis stimulating agents (ESAs).
It is estimated that 2.4 x 106 new erythrocytes should be produced each second to maintain adequate haematocrit in 5 L of blood of a healthy adult individual (2). Therefore, nearly 80% of average 25 mg of daily iron requirement is used for erythropoiesis (3). In physiological conditions daily intake of iron ranges from 10 to 15 mg and the maximum absorption is about 20%, thus normal diet provides only 2-3 mg of iron. The remaining part comes in greatest proportion from effete erythrocytes undergoing eryptosis (2). Iron deficiency has deleterious impact not only on tissue oxygenation through impaired haemoglobin synthesis, but also on various metabolic processes including accumulation of muscle energy or oxygen storage in myoglobin, neuron myelination, and DNA synthesis (4). According to American data from the National Health and Nutritional Examination Survey (NHANES III) 60-73% of persons with an estimated glomerular filtration rate < 60 ml/min/1.73 m2 are iron deficient, while iron deficiency anaemia affects 8.8% of the general world population (5, 6). Iron depletion is even more accentuated in patients with end-stage renal failure on maintenance haemodialysis, where blood loss during the procedure, frequent blood sampling and occult or overt gastrointestinal bleeding may diminish scant iron stores. Moreover, iron malabsorption may be exacerbated by poor appetite, low-protein diet and various drugs frequently used in CKD patients (proton pump inhibitors, phosphate binders). Despite absolute iron deficiency in CKD patients, functional iron deficiency (FID) is also prevalent. According to Macdougall’s definition, FID is a state in which there is insufficient iron incorporation into erythroid precursors in the face of apparently adequate iron stores (7). This applies to the partial block in iron transport being the major cause of anaemia of chronic disease observed in inflammatory, infectious and malignant diseases, and to the second type of FID frequently occurring when erythroid marrow is stimulated with ESAs (8). Albeit multifactorial, both absolute and functional iron deficiencies may be partly assigned to impaired hepcidin – ferroportin axis.
Hepcidin and ferroportin are two crucial proteins that in cooperation with hemojuvelin, hephaestin, iron transporter DMT1 and duodenal cytochrome B (Dcytb) regulate plasma iron concentration (9). Ferroportin is the only known mammalian iron exporter (10). This basolateral transmembrane efflux channel in combination with ferroxidases (hephaestin, ceruloplasmin) enables absorption of ferric ions from duodenal enterocytes. Apart from that, ferroportin facilitates transfer of iron from hepatocytic storage to plasma and retrieval of iron from macrophages of the mononuclear phagocyte system, which phagocyte senescent erythrocytes. Hepcidin in turn, is a peptide hormone produced by hepatocytes in response to increased iron levels. In a negative feedback loop hepcidin causes internalization and ubiquitination of ferroportin, thus limiting intestinal iron absorption and causing iron entrapment in macrophages, hepatocytes and enterocytes (11, 12). Decreased iron absorption is the only known mechanism preventing from iron overload, for iron loss is not regulated in any defined pathway and may occur mainly through cell shedding or bleeding (11, 13). Hence, hepcidin expression is modulated by various endogenous and exogenous factors. Tissue iron stores and transferrin saturation regulate hepcidin transcription by BMP-SMAD pathway with hemojuvelin as a co-factor. Inflammation is another hepcidin transcriptional regulator, through the JAK-STAT3 pathway initiated by Il-6 (12, 13). As a consequence, in numerous patients with chronic renal failure, hepcidin levels are elevated due to an underlying inflammatory process (14). Moreover, in the end-stage renal failure hepcidin may be not efficiently eliminated, neither by kidneys nor by dialysis. In addition, the dialysis procedure may initiate inflammatory-mediated hepcidin transcription (14). Therefore in CKD patients hepcidin levels consecutively rise, compromising iron homeostasis.
Taking into account all the pathophysiological aspects of iron absorption and storage in patients with CKD, screening for iron deficiency should be performed, and iron supplementation considered, especially in the view of poor responsiveness to ESA treatment.
Nevertheless, iron supplementation has certain disadvantages. Oral supplementation in CKD patients is frequently inefficient, while intravenous supplementation is associated with various adverse effects, including anaphylactic reactions and tissue toxicity. Iron is a redox-active transition metal and it may exist in two ionic states: ferrous – Fe(II), and ferric – Fe(III), thus enabling electron transfer among molecules. This redox activity is potentially damaging and free, unbound iron easily triggers it. Human organism limits free forms of iron ions by binding them to transferrin in plasma or to ferritin intracellularly, before incorporating it into heme and non-heme proteins (15, 16). Transferrin with two iron-binding sites may exist as four molecular forms – apotransferrin, monoferric A and B transferrin, and diferric transferrin, depending on the level of saturation (16). The saturation of transferrin is calculated with an equation:
TSAT = Fe (mg/dl)/TIBC(mg/dl) x 100%
and in physiological conditions ranges from 20 to 45%. Erythroblasts most efficiently utilize iron with TSAT 30-60%. Above this range macrophages intercept iron bound to transferrin and store it in ferritin (17, 18). Higher levels of transferrin saturation correspond to formation of significant amounts of non-transferrin bound iron (NTBI). This pool of free iron is supposed to be responsible for tissue toxicity and cell damage. NTBI via the Fenton and Haber-Weiss reactions, may induce oxidative stress by promoting formation of reactive oxygen species (ROS) that subsequently cause increased lipid, protein and carbohydrate peroxidation (19, 20). This in turn might result in disruption of cell membranes leading to their increased permeability or even cell lysis (4). In addition, iron dose-related damage to components of DNA was described (21). NTBI is absorbed mainly by the liver, however, an unregulated NTBI uptake was also observed in the cells of the endocrine system, the brain, lungs, or the heart (22, 23). Emerging data link NTBI to organ damage in iron-overload disorders, such as haemochromatosis or thalassaemia (24). Higher levels of TSAT, an evidence for reduced transferrin potential to buffer free iron pool, were associated with increased frequency of stomach cancer in women and colon cancer in men (25). Nevertheless, neither the pathophysiological consequences of short term increase of TSAT, observed after intravenous iron supplementation, nor long-term toxicity of repeated doses of iron preparations are known.
Currently in Europe there are several preparations used for intravenous iron supplementation: iron gluconate, ferric carboxymaltose, iron sucrose, iron low-molecular dextran, isomaltoside 1000, ferumoxytol. All these substances differ in size of molecules, pharmacokinetic and pharmacodynamic characteristics. Depending on the thermodynamic stability of the preparation, the pool of the labile iron, that is loosely attached to the transporting medium, and therefore immediately bound to transferrin after injection, is divers (4).
As injection of iron preparations results in the TSAT increase to various degrees, the aim of this study was to assess, how iron (III) isomaltoside 1000, a relatively new, stable iron preparation used in haemodialyzed patients as a part of routine supplementation, influences the saturation of transferrin.
Material and methods

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
  • Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
  • Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
  • Aby kupić kod proszę skorzystać z jednej z poniższych opcji.

Opcja #1


  • dostęp do tego artykułu
  • dostęp na 7 dni

uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony

Opcja #2


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 30 dni
  • najpopularniejsza opcja

Opcja #3


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 90 dni
  • oszczędzasz 28 zł
1. Tsiftsoglou AS, Vizirianakis IS, Strouboulis J: Erythropoiesis: Model Systems, Molecular Regulators, And Developmental Programs. IUBMB Life 2009; 61(8): 800-830.
2. Dzierzak E, Philipsen S: Erythropoiesis: development and differentiation. Cold Spring Harb Perspect Med 2013; 3(4): a011601.
3. Hentze MW, Muckenthaler MU, Andrews NC: Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117: 285-297.
4. Macdougall IC, Geisser P: Use of Intravenous Iron Supplementation in Chronic Kidney Disease. An Update IJKD 2013; 7: 9-22.
5. Fishbane S, Pollack S, Feldman HI, Joffe MM: Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988-2004. Clin J Am Soc Nephrol 2009; 4: 57-61.
6. Vos T, Flaxman AD, Naghavi M et al.: Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163-2196.
7. Macdougall IC, Hutton RD, Cavill I et al.: Poor response to treatment of renal anaemia with erythropoietin corrected by iron given intravenously. BMJ 1989; 299: 157-158.
8. Thomas DW, Hinchliffe RF, Briggs C et al.: Guideline for the laboratory diagnosis of functional iron deficiency. BJH 2013; 161: 639-648.
9. Ruchala P, Nemeth E: The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci 2014; 35(3): 155-161.
10. Nemeth E, Tuttle MS, Powelson J et al.: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306: 2090-2093.
11. Qiao B, Sugianto P, Fung E et al.: Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab 2012; 15: 918-924.
12. Babitt JL, Huang FW, Wrighting DM et al.: Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 2006; 38: 531-539.
13. Rishi G, Wallace DF, Subramaniam VN: Hepcidin: regulation of the master iron regulator. Biosci Rep 2015; 35(3): pii e00192.
14. Zumbrennen-Bullough K, Babitt JL: The iron cycle in chronic kidney disease (CKD): from genetics and experimental models to CKD patients. Nephrol Dial Transplant 2014; 29: 263-273.
15. McCord JM: Iron, Free radicals and Oxidative Injury. Semin Haematol 1998; 35: 5-12.
16. Brissot P, Ropert M, Le Lan C, Loreal O: Non-transferrin bound iron: A key role in iron overload and toxicity. Biochim Biophys Acta 2012; 3: 403-410.
17. Zadrazil J, Horak P: Pathophysiology of anemia in chronic kidney diseases: A review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015; 159(2): 197-202.
18. Besarab A, Coyne DW: Iron supplementation to treat anemia in patients with chronic kidney disease. Nat Rev Nephrol 2010; 6: 699-710.
19. Gutteridge JMC: Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Lett 1986; 201: 291-295.
20. Patel M, Ramavataram DVSS: Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation. Indian J Clin Biochem 2012; 27(4): 322-332.
21. Touati D, Jacques M, Tardat B et al.: Lethal oxidative damage and mutagenesis are generated by iron in Delta fur mutants of Escherichia coli: Protective role of superoxide dismutase. J Bacteriol 1995; 177: 2305-2314.
22. Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P: LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005; 18: 277-287.
23. Geisser P, Baer M, Schaub E: Structure/histoxicity relationship of parenteral iron preparations. Arzneimittelforschung 1992; 42: 1439-1452.
24. Piga A, Longo F, Duca L et al.: High nontransferrin bound iron levels and heart disease in thalassemia major. Am J Hematol 2009; 84: 29-33.
25. Herrinton LJ, Friedman GD, Baer D, Selby JV: Transferrin saturation and risk of cancer. Am J Epidemiol 1995; 142: 692-698.
26. Zager RA, Johnson AC, Hanson SY, Wasse H: Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 2002; 40(1): 90-103.
27. Kovesdy CP, Trivedi BK, Kalantar-Zadeh K, Anderson JE: Association of anemia with outcomes in men with moderate and severe chronic kidney disease. Kidney Int 2006; 69(3): 560-564.
28. Wells CW, Lewis S, Barton JR, Corbett S: Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflamm Bowel Dis 2006; 12(2): 123-130.
29. Johansen KL, Finkelstein FO, Revicki DA et al.: Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis stimulating agents. Am J Kidney Dis 2010; 55: 535-548.
30. Macdougall IC: Evolution of iv iron compounds over the last century. J Ren Care 2009; 35: 8-13.
31. Więcek A, Dębska-Ślizień A, Durlik M et al.: Leczenie niedokrwistości w chorobach nerek – Stanowisko Polskiego Towarzystwa Nefrologicznego. Nefrol Dial Pol 2015; 19: 12-26.
32. Gellert R, Żelek T, Daniewska D et al.: Suplementacja żelaza drogą dożylną w niedokrwistości nerkowopochodnej u pacjentów dializowanych – krytyczna ocena obecnej praktyki klinicznej w doświadczeniach jednego ośrodka. Post N Med 2011; 4: 337-343. 
otrzymano: 2015-09-02
zaakceptowano do druku: 2015-09-26

Adres do korespondencji:
*Ryszard Gellert
Department of Nephrology and Internal Medicine Center of Postgraduate Medical Education, P. Jerzy Popiełuszko Bielański Hospital
ul. Cegłowska 80, 01-809 Warszawa
tel. +48 (22) 569-02-06

Postępy Nauk Medycznych 10/2015
Strona internetowa czasopisma Postępy Nauk Medycznych