The labile side of iron supplementation in CKD

Journal of the American Society of Nephrology

Volumn 26, Issue 11, 2015, Pages 2612-2619

  Slotki, Itzchak ^a   Ioav Cabantchik, Zvi ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

IRON; ANTIANEMIC AGENT;

ADVERSE OUTCOME; ANEMIA; BIOACCUMULATION; CELL DAMAGE; CELL DEATH; CELL METABOLISM; CHRONIC KIDNEY DISEASE; CONTAMINATION; HUMAN; IRON BLOOD LEVEL; IRON METABOLISM; IRON OVERLOAD; IRON THERAPY; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; ADVERSE EFFECTS; ANEMIA, IRON-DEFICIENCY; ANIMAL; CLINICAL TRIAL (TOPIC); COMPLICATION; DIETARY SUPPLEMENT; HEMODIALYSIS; INFLAMMATION; INTRAVENOUS DRUG ADMINISTRATION; KIDNEY FAILURE, CHRONIC; MACROPHAGE; METABOLISM; ORAL DRUG ADMINISTRATION; RISK FACTOR;

ADMINISTRATION, INTRAVENOUS; ADMINISTRATION, ORAL; ANEMIA, IRON-DEFICIENCY; ANIMALS; CLINICAL TRIALS AS TOPIC; DIETARY SUPPLEMENTS; HEMATINICS; HUMANS; INFLAMMATION; IRON; KIDNEY FAILURE, CHRONIC; MACROPHAGES; OXIDATIVE STRESS; RENAL DIALYSIS; RISK FACTORS;

EID: 84937585342     PISSN: 10466673     EISSN: 15333450     Source Type: Journal    
DOI: 10.1681/ASN.2015010052     Document Type: Review

References (93)

1. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA: The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339: 584-590, 1998
2. Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A; CREATE Investigators: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355: 2071-2084, 2006
3. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355: 2085-2098, 2006
4. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R; TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361: 2019-2032, 2009
5. KDIGOAnemiaWork Group: KDIGOClinical Practice Guidelines for Anemia in Chronic Kidney Disease. Kidney Int Suppl 2: 1-335, 2012
6. Auerbach M, Macdougall IC: Safety of intravenous iron formulations: facts and folklore. Blood Transfus 12: 296-300, 2014
7. Fishbane S, Mathew AT, Wanchoo R: Intravenous iron exposure and outcomes in patients on hemodialysis. Clin J AmSoc Nephrol 9: 1837-1839, 2014
8. Martines AM, Masereeuw R, Tjalsma H, Hoenderop JG, Wetzels JF, Swinkels DW: Iron metabolism in the pathogenesis of iron-induced kidney injury. Nat Rev Nephrol 9: 385-398, 2013
9. Crichton R: Inorganic Biochemistry of Iron Metabolism: FromMolecular Mechanisms to Clinical Consequences, 2nd Ed., Chichester, Wiley, 2014
10. Wang J, Pantopoulos K: Regulation of cellular iron metabolism. BiochemJ 434: 365-381, 2011
11. Rouault TA: The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2: 406-414, 2006
12. Ganz T: Systemic iron homeostasis. Physiol Rev 93: 1721-1741, 2013
13. Gammella E, Buratti P, Cairo G, Recalcati S: Macrophages: central regulators of iron balance. Metallomics 6: 1336-1345, 2014
14. Halliwell B, Gutteridge JM: Free Radicals in Biology and Medicine, 4th Ed., London, Oxford University Press, 2007
15. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR: Ferroptosis: an irondependent form of nonapoptotic cell death. Cell 149: 1060-1072, 2012
16. Cabantchik ZI, Sohn YS, Breuer W, Esposito B: The molecular and cellular basis of iron toxicity in iron overload disorders. Diagnostic and therapeutic approaches. Thalassemia Rep 3: e3, 2013
17. Camaschella C: Hereditary sideroblastic anemias: pathophysiology, diagnosis, and treatment. Semin Hematol 46: 371-377, 2009
18. Fleming RE, Ponka P: Iron overload in human disease. N Engl J Med 366: 348-359, 2012
19. Wood JC: Magnetic resonance imaging measurement of iron overload. CurrOpin Hematol 14: 183-190, 2007
20. Picard V, Epsztejn S, Santambrogio P, Cabantchik ZI, Beaumont C: Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells. JBiolChem273: 15382 15386, 1998
21. Cabantchik ZI: Labile iron in cells and body fluids: physiology, pathology, and pharmacology. Front Pharmacol 5: 45, 2014
22. Jacobs A: Low molecular weight intracellular iron transport compounds. Blood 50: 433-439, 1977
23. Kruszewski M: Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat Res 531: 81-92, 2003
24. Glickstein H, El RB, Shvartsman M, Cabantchik ZI: Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 106: 3242-3250, 2005
25. KakhlonO,Manning H, BreuerW,Melamed Book N, Lu C, Cortopassi G, Munnich A, Cabantchik ZI: Cell functions impaired by frataxin deficiency are restored by drugmediated iron relocation. Blood 112: 5219 5227, 2008
26. Sohn YS, Breuer W, Munnich A, Cabantchik ZI: Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications. Blood 111: 1690-1699, 2008
27. Hershko C, GrahamG, BatesGW, Rachmilewitz EA:Non-specific serumiron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol 40: 255-263, 1978
28. Breuer W, Hershko C, Cabantchik ZI: The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci 23: 185-192, 2000
29. Brissot P, RopertM, Le Lan C, Loréal O: Nontransferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta 1820: 403-410, 2012
30. Singh S, Hider RC, Porter JB: A direct method for quantification of non-transferrin-bound iron. Anal Biochem 186: 320-323, 1990
31. Kolb AM, Smit NP, Lentz-Ljuboje R, Osanto S, van Pelt J: Non-transferrin bound iron measurement is influenced by chelator concentration. Anal Biochem 385: 13-19, 2009
32. Lee DH, Liu DY, Jacobs DR Jr, Shin HR, Song K, Lee IK, Kim B, Hider RC: Common presence of non-transferrin-bound iron among patients with type 2 diabetes. Diabetes Care 29: 1090-1095, 2006
33. SilvaAM,HiderRC: Influenceofnon-enzymatic post-translation modifications on the ability of human serum albumin to bind iron. Implications for non-transferrin-bound iron speciation. Biochim Biophys Acta 1794: 1449-1458, 2009
34. Kooistra MP, Kersting S, Gosriwatana I, Lu S, Nijhoff-Schutte J, Hider RC, Marx J-JM: Nontransferrin-bound iron in the plasma of haemodialysis patients after intravenous iron saccharate infusion. Eur JClin Invest 32[Suppl 1]: 36-41, 2002
35. Espósito BP, Breuer W, Slotki I, Cabantchik ZI: Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin bound iron in dialysis patients. Eur J Clin Invest 32[Suppl 1]: 42-49, 2002
36. Halliwell B, Aruoma OI, Mufti G, Bomford A: Bleomycin-detectable iron in serum from leukaemic patients before and after chemotherapy. Therapeutic implications for treatment with oxidant-generating drugs. FEBS Lett 241: 202-204, 1988
37. Zanninelli G, Breuer W, Cabantchik ZI: Daily labile plasma iron as an indicator of chelator activity in Thalassaemia major patients. Br J Haematol 147: 744-751, 2009
38. Danjou F, Cabantchik ZI, Origa R, Moi P, Marcias M, Barella S, Defraia E, Desso C, Foschini ML, Giagu N, Leoni GB, Morittu M, Galanello R: A decisional algorithm to start iron chelation in patients with beta thalassemia. Haematologica 99: e38-e40, 2014
39. Van Buren P, Velez RL, Vaziri ND, Zhou XJ: Iron overdose: a contributor to adverse outcomes in randomized trials of anemia correction in CKD. Int Urol Nephrol 44: 499 507, 2012
40. Gordon S, Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol 5: 953-964, 2005
41. Ishida JH, Johansen KL: Iron and infection in hemodialysis patients. Semin Dial 27: 26-36, 2014
42. Mencacci A, Cenci E, Boelaert JR, Bucci P, Mosci P, Fo d'Ostiani C, Bistoni F, Romani L: Iron overload alters innate and T helper cell responses to Candida albicans in mice. J Infect Dis 175: 1467-1476, 1997
43. Charytan DM, Pai AB, Chan CT, Coyne DW, HungAM, KovesdyCP, Fishbane S; on behalf of the Dialysis Advisory Group of the American Society of Nephrology: Considerations and challenges in defining optimal iron utilization in hemodialysis [published online ahead of print xxxx xx, 2014]. J Am Soc Nephrol pii: ASN.2014090922
44. Feldman HI, Santanna J, Guo W, Furst H, Franklin E, Joffe M, Marcus S, Faich G: Iron administration and clinical outcomes in hemodialysis patients. J Am Soc Nephrol 13: 734-744, 2002
45. Feldman HI, Joffe M, Robinson B, Knauss J, Cizman B, Guo W, Franklin-Becker E, Faich G: Administration of parenteral iron and mortality among hemodialysis patients.JAm Soc Nephrol 15: 1623-1632, 2004
46. Kalantar-Zadeh K, Regidor DL, McAllister CJ,Michael B, Warnock DG: Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol 16: 3070-3080, 2005
47. Kuo KL, Hung SC, Lin YP, Tang CF, Lee TS, Lin CP, Tarng DC: Intravenous ferric chloride hexahydrate supplementation induced endothelial dysfunction and increased cardiovascular risk among hemodialysis patients. PLoS ONE 7: e50295, 2012
48. Kuragano T, Matsumura O, Matsuda A, Hara T, Kiyomoto H, Murata T, Kitamura K, Fujimoto S, Hase H, Joki N, Fukatsu A, Inoue T, Itakura I, Nakanishi T: Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kidney Int 86: 845 854, 2014
49. BailieGR, LarkinaM,GoodkinDA, Li Y, Pisoni RL, Bieber B, Mason N, Tong L, Locatelli F, Marshall MR, Inaba M, Robinson BM: Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality. Kidney Int 87: 162-168, 2015
50. Miskulin DC, Tangri N, Bandeen-Roche K, Zhou J, McDermott A, Meyer KB, Ephraim PL, Michels WM, Jaar BG, Crews DC, Scialla JJ, Sozio SM, Shafi T, Wu AW, Cook C, Boulware LE; Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network Patient Outcomes in End Stage Renal Disease Study Investigators: Intravenous iron exposure and mortality in patients on hemodialysis. Clin J Am Soc Nephrol 9: 1930 1939, 2014
51. Kshirsagar AV, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Brookhart MA: Intravenous iron supplementation practices and short-term risk of cardiovascular events in hemodialysis patients. PLoS ONE 8: e78930, 2013
52. Goodkin DA, Bragg-Gresham JL, Koenig KG, Wolfe RA, Akiba T, Andreucci VE, Saito A, Rayner HC, Kurokawa K, Port FK, Held PJ, Young EW: Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS). J Am Soc Nephrol 14: 3270-3277, 2003
53. Brookhart MA, Freburger JK, Ellis AR, Wang L,WinkelmayerWC, Kshirsagar AV: Infection risk with bolus versus maintenance iron supplementation in hemodialysis patients. J Am Soc Nephrol 24: 1151-1158, 2013
54. Sirken G, Raja R, Rizkala AR: Association of different intravenous iron preparations with risk of bacteremia in maintenance hemodialysis patients. Clin Nephrol 66: 348-356, 2006
55. Drüeke T,Witko-Sarsat V,Massy Z,Descamps Latscha B,Guerin AP, Marchais SJ, Gausson V, LondonGM: Iron therapy, advanced oxidation protein products, and carotid artery intimamedia thickness in end-stage renal disease. Circulation 106: 2212-2217, 2002
56. Coyne DW, Kapoian T, Suki W, Singh AK, Moran JE, Dahl NV, Rizkala AR; DRIVE Study Group: Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study. J Am Soc Nephrol 18: 975 984, 2007
57. Kapoian T, O'Mara NB, Singh AK, Moran J, Rizkala AR, Geronemus R, Kopelman RC, Dahl NV, Coyne DW: Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin. J Am Soc Nephrol 19: 372-379, 2008
58. Besarab A, Amin N, Ahsan M, Vogel SE, Zazuwa G, Frinak S, Zazra JJ, Anandan JV, Gupta A:Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients. J Am Soc Nephrol 11: 530-538, 2000
59. Auryxia (ferric citrate) tablets. 2015. 11-1-2015.
60. Lewis JB, Sika M, Koury MJ, Chuang P, Schulman G, Smith MT, Whittier FC, Linfert DR, Galphin CM, Athreya BP, Nossuli AK, Chang IJ, Blumenthal SS, Manley J, Zeig S, Kant KS, Olivero JJ, Greene T, Dwyer JP; Collaborative Study Group: Ferric citrate controls phosphorus and delivers iron in patients on dialysis. J Am Soc Nephrol 26: 493-503, 2015
61. Mercadel L, Metzger M, Haymann JP, Thervet E, Boffa JJ, Flamant M, Vrtovsnik F, Houillier P, Froissart M, Stengel B;NephroTest Study Group: The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease. PLoSONE9: e99781, 2014
62. Vaziri ND: Understanding iron: promoting its safe use in patients with chronic kidney failure treated by hemodialysis.AmJ KidneyDis 61: 992-1000, 2013
63. Weiss G, Kronenberg F: Intravenous iron administration: new observations and time for the next steps. Kidney Int 87: 10-12, 2015
64. Kuo KL, Hung SC, Lee TS, Tarng DC: Iron sucrose accelerates early atherogenesis by increasing superoxide production and upregulating adhesion molecules in CKD. J Am Soc Nephrol 25: 2596-2606, 2014
65. Lim PS, Wei YH, Yu YL, Kho B: Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 14: 2680-2687, 1999
66. Descamps-Latscha B, Witko-Sarsat V: Importance of oxidatively modified proteins in chronic renal failure. Kidney Int Suppl 78: S108-S113, 2001
67. AnrakuM, Kitamura K, Shinohara A, AdachiM, Suenga A, Maruyama T, Miyanaka K, Miyoshi T, ShiraishiN,Nonoguchi H, OtagiriM, Tomita K: Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients. Kidney Int 66: 841-848, 2004
68. Michelis R, Gery R, Sela S, Shurtz-Swirski R, Grinberg N, Snitkovski T, Shasha SM, Kristal B: Carbonyl stress induced by intravenous iron during haemodialysis. Nephrol Dial Transplant 18: 924-930, 2003
69. Himmelfarb J,McMonagle E,McMenamin E: Plasma protein thiol oxidation and carbonyl formation in chronic renal failure. Kidney Int 58: 2571-2578, 2000
70. SezerMT,AkinH,Demir M, Erturk J, Aydin ZD, Savik E, Tunc N: The effect of serum albumin level on iron-induced oxidative stress in chronic renal failure patients. J Nephrol 20: 196-203, 2007
71. Pai AB, Boyd AV, McQuade CR, Harford A, Norenberg JP, Zager PG: Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis. Pharmacotherapy 27: 343-350, 2007
72. Pai AB, Conner T,McQuade CR,Olp J, Hicks P: Non-transferrin bound iron, cytokine activation and intracellular reactive oxygen species generation in hemodialysis patients receiving intravenous iron dextran or iron sucrose. Biometals 24: 603-613, 2011
73. Parkkinen J, von Bonsdorff L, Peltonen S, Grönhagen-Riska C, Rosenlöf K: Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. ironsaccharate administration. Nephrol Dial Transplant 15: 1827-1834, 2000
74. Barton Pai A, Pai MP, Depczynski J, McQuade CR, Mercier RC: Non-transferrinbound iron is associated with enhanced Staphylococcus aureus growth in hemodialysis patients receiving intravenous iron sucrose. Am J Nephrol 26: 304-309, 2006
75. Rangel EB, Espósito BP, Carneiro FD, Mallet AC, Matos AC, Andreoli MC, Guimaries Souza NK, Santos BF: Labile plasma iron generation after intravenous iron is timedependent and transitory in patients undergoing chronic hemodialysis. Ther Apher Dial 14: 186-192, 2010
76. Van Wyck D, Anderson J, Johnson K: Labile iron in parenteral iron formulations: a quantitative and comparative study. Nephrol Dial Transplant 19: 561-565, 2004
77. Rooyakkers TM, Stroes ES, Kooistra MP, van Faassen EE, Hider RC, Rabelink TJ, Marx JJ: Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest 32[Suppl 1]: 9-16, 2002
78. Tovbin D, Mazor D, Vorobiov M, Chaimovitz C, Meyerstein N: Induction of protein oxidation by intravenous iron in hemodialysis patients: role of inflammation. Am J Kidney Dis 40: 1005-1012, 2002
79. Canavese C, Bergamo D, Ciccone G, Longo F, Fop F, Thea A, Martina G, Piga A: Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients. Kidney Int 65: 1091-1098, 2004
80. Rostoker G, Griuncelli M, Loridon C, Couprie R, Benmaadi A, Bounhiol C, Roy M, Machado G, Janklewicz P, Drahi G, Dahan H, Cohen Y: Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: aMRI study. Am J Med 125: 991-999. e1, 2012
81. McLarenGD,MuirWA, Kellermeyer RW: Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. Crit RevClin Lab Sci 19: 205-266, 1983
82. Ghoti H, Rachmilewitz EA, Simon-Lopez R, Gaber R, Katzir Z, Konen E, Kushnir T, Girelli D, Campostrini N, Fibach E, Goitein O: Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol 89: 87-93, 2012
83. Johnson AC, Becker K, Zager RA: Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury. Am J Physiol Renal Physiol 299: F426-F435, 2010
84. LimCS, Vaziri ND: The effects of iron dextran on the oxidative stress in cardiovascular tissues of rats with chronic renal failure. Kidney Int 65: 1802-1809, 2004
85. Fütterer S, Andrusenko I, Kolb U, Hofmeister W, Langguth P: Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X-ray powder diffraction (XRPD). J Pharm Biomed Anal 86: 151-160, 2013
86. JahnMR, Andreasen HB, Fütterer S, Nawroth T, Schünemann V, Kolb U, Hofmeister W, Muñoz M, Bock K, Meldal M, Langguth P: A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm 78: 480-491, 2011
87. Scheiber-Mojdehkar B, Lutzky B, Schaufler R, Sturm B, Goldenberg H: Non-transferrinbound iron in the serum of hemodialysis patients who receive ferric saccharate: no correlation to peroxide generation.JAmSoc Nephrol 15: 1648-1655, 2004
88. Macdougall IC: Evolution of iv iron compounds over the last century. J Ren Care 35 [Suppl 2]: 8-13, 2009
89. Bishu K, Agarwal R: Acute injury with intravenous iron and concerns regarding long-term safety. Clin J Am Soc Nephrol 1 [Suppl 1]: S19-S23, 2006
90. Malindretos P, Sarafidis PA, Rudenco I, Raptis V, Makedou K, Makedou A, Grekas DM: Slow intravenous iron administration does not aggravate oxidative stress and inflammatory biomarkers during hemodialysis: a comparative study between iron sucrose and iron dextran.AmJNephrol 27: 572-579, 2007
91. Styskal J, Van Remmen H, Richardson A, Salmon AB: Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free Radic Biol Med 52: 46-58, 2012
92. Guida C, Altamura S, Klein FA, Galy B, Boutros M, Ulmer AJ, Hentze MW, Muckenthaler MU: A novel inflammatory pathway mediating rapid hepcidin-independent hypoferremia. Blood 125: 2265-2275, 2015
93. Finberg KE: Ironing out the role of Toll-like receptors. Blood 125: 2183-2184, 2015