Iron and anemia in human biology: A review of mechanisms

Heart Failure Reviews

Volumn 13, Issue 4, 2008, Pages 393-404

  Handelman, Garry J ^a,b   Levin, Nathan W ^b  

^a UNIVERSITY OF MASSACHUSETTS LOWELL   (United States)

^b RENAL RESEARCH INSTITUTE   (United States)

Author keywords

Anemia; Erythropoietin; Heart failure; Hepcidin; Inflammation; Iron

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; ASCORBIC ACID; ATLIZUMAB; C REACTIVE PROTEIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; ERYTHROPOIETIN; FERRITIN; FERROPORTIN; HEMOGLOBIN; HEPCIDIN; INTERLEUKIN 6; IRON; NONSTEROID ANTIINFLAMMATORY AGENT; RECOMBINANT ERYTHROPOIETIN; TRANSFERRIN; TRANSFERRIN RECEPTOR; VALSARTAN;

ADJUVANT THERAPY; ANEMIA; BLEEDING; BONE MARROW; CELL AGING; CHRONIC DISEASE; CLINICAL TRIAL; DIET SUPPLEMENTATION; DRUG DOSE INCREASE; ERYTHROCYTE; ERYTHROPOIESIS; FERRITIN BLOOD LEVEL; GASTROINTESTINAL HEMORRHAGE; HEART FAILURE; HEMODIALYSIS PATIENT; HUMAN; INFLAMMATION; IRON BLOOD LEVEL; IRON DEFICIENCY ANEMIA; IRON METABOLISM; IRON STORAGE; IRON THERAPY; IRON TRANSPORT; KIDNEY DISEASE; NUTRITION; PLASMA VOLUME; REVIEW; TREATMENT FAILURE;

ANEMIA; ANEMIA, IRON-DEFICIENCY; CHRONIC DISEASE; EPOETIN ALFA; FEMALE; HEART DISEASES; HEMATINICS; HUMANS; INFLAMMATION; IRON; KIDNEY DISEASES; MALE;

EID: 43749090222     PISSN: 13824147     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10741-008-9086-x     Document Type: Review

References (119)

1. Cook JD, Barry WE, Hershko C, Fillet G, Finch CA (1973) Iron kinetics with emphasis on iron overload. Am J Pathol 72:337-343
2. Bullen JJ, Rogers HJ, Spalding PB, Ward CG (2006) Natural resistance, iron and infection: A challenge for clinical medicine. J Med Microbiol 55:251-258
3. Roque ME, Sandoval MJ, Aggio MC (2001) Serum erythropoietin and its relation with soluble transferrin receptor in patients with different types of anaemia in a locally defined reference population. Clin Lab Haematol 23:291-295
4. Erdem A, Erdem M, Arslan M, Yazici G, Eskandari R, Himmetoglu O (2002) The effect of maternal anemia and iron deficiency on fetal erythropoiesis: Comparison between serum erythropoietin, hemoglobin and ferritin levels in mothers and newborns. J Matern Fetal Neonatal Med 11:329-332
5. Artunc F, Risler T (2007) Serum erythropoietin concentrations and responses to anaemia in patients with or without chronic kidney disease. Nephrol Dial Transplant 10:2900-2908
6. Remy I, Wilson IA, Michnick SW (1999) Erythropoietin receptor activation by a ligand-induced conformation change. Science 283:990-993
7. Gordeuk VR, Bacon BR, Brittenham GM (1987) Iron overload: Causes and consequences. Annu Rev Nutr 7:485-508
8. Cook JD, Flowers CH, Skikne BS (2003) The quantitative assessment of body iron. Blood 101:3359-3364
9. Brownlie Tt, Utermohlen V, Hinton PS, Haas JD (2004) Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. Am J Clin Nutr 79:437-443
10. Walters GO, Miller FM, Worwood M (1973) Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol 26:770-772
11. Cook JD (1982) Clinical evaluation of iron deficiency. Semin Hematol 19:6-18
12. Skikne BS, Flowers CH, Cook JD (1990) Serum transferrin receptor: A quantitative measure of tissue iron deficiency. Blood 75:1870-1876
13. Labbe RF, Dewanji A (2004) Iron assessment tests: Transferrin receptor vis-a-vis zinc protoporphyrin. Clin Biochem 37:165-174
14. Vernet M, Doyen C (2000) Assessment of iron status with a new fully automated assay for transferrin receptor in human serum. Clin Chem Lab Med 38:437-442
15. Brugnara C, Schiller B, Moran J (2006) Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states. Clin Lab Haematol 28:303-308
16. Bakr AF, Sarette G (2006) Measurement of reticulocyte hemoglobin content to diagnose iron deficiency in Saudi children. Eur J Pediatr 165:442-445
17. Kotisaari S, Romppanen J, Penttila I, Punnonen K (2002) The Advia 120 red blood cells and reticulocyte indices are useful in diagnosis of iron-deficiency anemia. Eur J Haematol 68:150-156
18. Harthoorn-Lasthuizen EJ, Lindemans J, Langenhuijsen MM (1998) Zinc protoporphyrin as screening test in female blood donors. Clin Chem 44:800-804
19. Lorentz A, Jendrissek A, Eckardt KU, Schipplick M, Osswald PM, Kurtz A (1991) Serial immunoreactive erythropoietin levels in autologous blood donors. Transfusion 31:650-654
20. Bovy C, Gothot A, Delanaye P, Warling X, Krzesinski JM, Beguin Y (2007) Mature erythrocyte parameters as new markers of functional iron deficiency in haemodialysis: Sensitivity and specificity. Nephrol Dial Transplant 22:1156-1162
21. Rybo E, Bengtsson C (1985) Sideroblast count and examination of bone marrow reticuloendothelial iron in the diagnosis of iron deficiency. Scand J Haematol Suppl 43:77-85
22. Murray-Kolb LE, Beard JL (2007) Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr 85:778-787
23. Hallberg L, Hulthen L (2000) Prediction of dietary iron absorption: An algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 71:1147-1160
24. Brugnara C, Laufer MR, Friedman AJ, Bridges K, Platt O (1994) Reticulocyte hemoglobin content (CHr): Early indicator of iron deficiency and response to therapy. Blood 83:3100-3101
25. Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352:1011-1023
26. Olthof AW, Sijens PE, Kreeftenberg HG, Kappert P, Irwan R, van der Jagt EJ, Oudkerk M (2007) Correlation between serum ferritin levels and liver iron concentration determined by MR imaging: Impact of hematologic disease and inflammation. Magn Reson Imaging 25:228-231
27. Cazzola M, Ponchio L, de Benedetti F, Ravelli A, Rosti V, Beguin Y, Invernizzi R, Barosi G, Martini A (1996) Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. Blood 87:4824-4830
28. Thomas C, Thomas L (2005) Anemia of chronic disease: Pathophysiology and laboratory diagnosis. Lab Hematol 11:14-23
29. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271-1276
30. Cooper AC, Mikhail A, Lethbridge MW, Kemeny DM, Macdougall IC (2003) Increased expression of erythropoiesis inhibiting cytokines (IFN-gamma, TNF-alpha, IL-10, and IL-13) by T cells in patients exhibiting a poor response to erythropoietin therapy. J Am Soc Nephrol 14:1776-1784
31. Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M (2005) Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci USA 102:1324-1328
32. Tomosugi N, Kawabata H, Wakatabe R, Higuchi M, Yamaya H, Umehara H, Ishikawa I (2006) Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System. Blood 108:1381-1387
33. Kemna EH, Tjalsma H, Podust VN, Swinkels DW (2007) Mass spectrometry-based hepcidin measurements in serum and urine: Analytical aspects and clinical implications. Clin Chem 53:620-628
34. Murphy AT, Witcher DR, Luan P, Wroblewski VJ (2007) Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. Blood 110:1048-1054
35. Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448-454
36. Thomas C, Kirschbaum A, Boehm D, Thomas L (2006) The diagnostic plot: A concept for identifying different states of iron deficiency and monitoring the response to epoetin therapy. Med Oncol 23:23-36
37. Wians FH Jr, Urban JE, Keffer JH, Kroft SH (2001) Discriminating between iron deficiency anemia and anemia of chronic disease using traditional indices of iron status vs transferrin receptor concentration. Am J Clin Pathol 115:112-118
38. Nishimoto N, Kishimoto T (2006) Interleukin 6: From bench to bedside. Nat Clin Pract Rheumatol 2:619-626
39. Park CH, Valore EV, Waring AJ, Ganz T (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806-7810
40. Canavese C, Bergamo D, Ciccone G, Burdese M, Maddalena E, Barbieri S, Thea A, Fop F (2004) Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients. Nephrol Dial Transplant 19:1564-1570
41. Peter J, Finkelstein F (2006) The effectiveness of low-dose maintenance i.v. iron therapy: A dialysis facility's experience. Nephrol Nurs J 33:71-74, 90
42. Brockmoller J, Kochling J, Weber W, Looby M, Roots I, Neumayer HH (1992) The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients. Br J Clin Pharmacol 34:499-508
43. Gladziwa U, Klotz U, Baumer K, Zollinger R, Mann H, Sieberth HG (1993) Pharmacokinetics of epoetin (recombinant human erythropoietin) after long term therapy in patients undergoing haemodialysis and haemofiltration. Clin Pharmacokinet 25:145-153
44. Cahan C, Decker MJ, Arnold JL, Washington LH, Veldhuis JD, Goldwasser E, Strohl KP (1992) Diurnal variations in serum erythropoietin levels in healthy subjects and sleep apnea patients. J Appl Physiol 72:2112-2117
45. Macdougall IC (2006) Recent advances in erythropoietic agents in renal anemia. Semin Nephrol 26:313-318
46. Macdougall IC, Padhi D, Jang G (2007) Pharmacology of darbepoetin alfa. Nephrol Dial Transplant 22(Suppl 4):iV2-iv9
47. Handelman GJ, Walter MF, Adhikarla R, Gross J, Dallal GE, Levin NW, Blumberg JB (2001) Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney Int 59:1960-1966
48. Yeun JY, Levine RA, Mantadilok V, Kaysen GA (2000) C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kid Dis 35:469-476
49. Canavese C, Bergamo D, Ciccone G, Longo F, Fop F, Thea A, Martina G, Piga A (2004) Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients. Kidney Int 65:1091-1098
50. MacFie J (2004) Current status of bacterial translocation as a cause of surgical sepsis. Br Med Bull 71:1-11
51. Kotanko P, Carter M, Levin NW (2006) Intestinal bacterial microflora-a potential source of chronic inflammation in patients with chronic kidney disease. Nephrol Dial Transplant 21:2057-2060
52. Coyne DW, Kapoian T, Suki W, Singh AK, Moran JE, Dahl NV, Rizkala AR (2007) 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
53. Flaharty KK, Caro J, Erslev A, Whalen JJ, Morris EM, Bjornsson TD, Vlasses PH (1990) Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men. Clin Pharmacol Ther 47:557-564
54. Uehlinger DE, Gotch FA, Sheiner LB (1992) A pharmacodynamic model of erythropoietin therapy for uremic anemia. Clin Pharmacol Ther 51:76-89
55. Means RT Jr (1999) Advances in the anemia of chronic disease. Int J Hematol 70:7-12
56. Handelman GJ (2007) Vitamin C deficiency in dialysis patients-are we perceiving the tip of an iceberg? Nephrol Dial Transplant 22:328-331
57. Deicher R, Ziai F, Bieglmayer C, Schillinger M, Horl WH (2005) Low total vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in hemodialysis patients. J Am Soc Nephrol 16:1811-1818
58. Handelman GJ (2006) Vitamin C deficiency in dialysis patients - are we perceiving the tip of an iceberg? Nephrol Dial Transplant 22:328-331
59. Wang S, Geraci G, Kuhlmann MK, Levin NW, Handelman GJ (2007) Chemical reactions of vitamin C with intravenous-iron formulations. Nephrol Dial Transplant 23:120-125
60. Anand I, McMurray JJ, Whitmore J, Warren M, Pham A, McCamish MA, Burton PB (2004) Anemia and its relationship to clinical outcome in heart failure. Circulation 110:149-154
61. Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, Chiang YT, Aknay N, Maggioni AP, Opasich C, Latini R, Cohn JN (2005) Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: Results from Val-HeFT. Circulation 112:1121-1127
62. Maggioni AP, Opasich C, Anand I, Barlera S, Carbonieri E, Gonzini L, Tavazzi L, Latini R, Cohn J (2005) Anemia in patients with heart failure: Prevalence and prognostic role in a controlled trial and in clinical practice. J Card Fail 11:91-98
63. Tang YD, Katz SD (2006) Anemia in chronic heart failure: Prevalence, etiology, clinical correlates, and treatment options. Circulation 113:2454-2461
64. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Borenstein J (2002) Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol 39:1780-1786
65. Felker GM, Gattis WA, Leimberger JD, Adams KF, Cuffe MS, Gheorghiade M, O'Connor CM (2003) Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 92:625-628
66. Paul S, Paul RV (2004) Anemia in heart failure: Implications, management, and outcomes. J Cardiovasc Nurs 19:S57-S66
67. Ezekowitz JA, McAlister FA, Armstrong PW (2003) Anemia is common in heart failure and is associated with poor outcomes: Insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 107:223-225
68. Gunnell J, Yeun JY, Depner TA, Kaysen GA (1999) Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 33:63-72
69. Anand IS, Latini R, Florea VG, Kuskowski MA, Rector T, Masson S, Signorini S, Mocarelli P, Hester A, Glazer R, Cohn JN (2005) C-reactive protein in heart failure: Prognostic value and the effect of valsartan. Circulation 112:1428-1434
70. Berry C, Norrie J, Hogg K, Brett M, Stevenson K, McMurray JJ (2006) The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 151:1313-1321
71. Srivastava PM, Thomas MC, Calafiore P, MacIsaac RJ, Jerums G, Burrell LM (2006) Diastolic dysfunction is associated with anaemia in patients with Type II diabetes. Clin Sci (Lond) 110:109-116
72. Windram JD, Loh PH, Rigby AS, Hanning I, Clark AL, Cleland JG (2007) Relationship of high-sensitivity C-reactive protein to prognosis and other prognostic markers in outpatients with heart failure. Am Heart J 153:1048-1055
73. Bolger AP, Bartlett FR, Penston HS, O'Leary J, Pollock N, Kaprielian R, Chapman CM (2006) Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 48:1225-1227
74. Toblli JE, Lombrana A, Duarte P, Di Gennaro F (2007) Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 50:1657-1665
75. Ohsugi Y (2007) Recent advances in immunopathophysiology of interleukin-6: An innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases. Biol Pharm Bull 30:2001-2006
76. van der Meer P, Voors AA, Lipsic E, Smilde TD, van Gilst WH, van Veldhuisen DJ (2004) Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 44:63-67
77. Silva RP, Barbosa PH, Kimura OS, Sobrinho CR, Sousa Neto JD, Silva FA, Silva Junior GB, Mota RM, Daher EF (2007) Prevalance of anemia and its association with cardio-renal syndrome. Int J Cardiol 120:232-236
78. de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, Bhandari S, Clark AL, Cleland JG (2006) Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 98:391-398
79. Witte KK, Desilva R, Chattopadhyay S, Ghosh J, Cleland JG, Clark AL (2004) Are hematinic deficiencies the cause of anemia in chronic heart failure? Am Heart J 147:924-930
80. Opasich C, Cazzola M, Scelsi L, De Feo S, Bosimini E, Lagioia R, Febo O, Ferrari R, Fucili A, Moratti R, Tramarin R, Tavazzi L (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26:2232-2237
81. Androne AS, Hryniewicz K, Hudaihed A, Mancini D, Lamanca J, Katz SD (2004) Relation of unrecognized hypervolemia in chronic heart failure to clinical status, hemodynamics, and patient outcomes. Am J Cardiol 93:1254-1259
82. Westenbrink BD, Visser FW, Voors AA, Smilde TD, Lipsic E, Navis G, Hillege HL, van Gilst WH, van Veldhuisen DJ (2007) Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J 28:166-171
83. van der Meer P, Lipsic E, Westenbrink BD, van de Wal RM, Schoemaker RG, Vellenga E, van Veldhuisen DJ, Voors AA, van Gilst WH (2005) Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation 112:1743-1747
84. Terrovitis JV, Anastasiou-Nana MI, Alexopoulos GP, Tsolakis EJ, Margari ZJ, Drakos SG, Tsagalou EP, Papazoglou P, Efentakis S, Nanas JN (2006) Prevalence and prognostic significance of anemia in patients with congestive heart failure treated with standard vs high doses of enalapril. J Heart Lung Transplant 25:333-338
85. Kotanko P (1996) Intensity of hemodialysis and response to erythropoietin. N Engl J Med 334:1670; author reply 1670-1671
86. Le Meur Y, Lorgeot V, Comte L, Szelag JC, Aldigier JC, Leroux-Robert C, Praloran V (2001) Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: Relationship with erythropoietin requirements. Am J Kidney Dis 38:510-517
87. ELISA assay for N-acetyl-serylaspartyl-lysyl-proline (Ac-SDKP). Cayman Chemical Company, Ann Arbor, MI
88. Volpe M, Tritto C, Testa U, Rao MA, Martucci R, Mirante A, Enea I, Russo R, Rubattu S, Condorelli GL, et al (1994) Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles. Am J Cardiol 74:468-473
89. Julian BA, Brantley RR Jr, Barker CV, Stopka T, Gaston RS, Curtis JJ, Lee JY, Prchal JT (1998) Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in posttransplant erythrocytosis. J Am Soc Nephrol 9:1104-1108
90. Freudenthaler SM, Lucht I, Schenk T, Brink M, Gleiter CH (2000) Dose-dependent effect of angiotensin II on human erythropoietin production. Pflugers Arch 439:838-844
91. Guyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R (1990) Diagnosis of iron-deficiency anemia in the elderly. Am J Med 88:205-209
92. Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD (1992) Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med 119:385-390
93. Annibale B, Capurso G, Delle Fave G (2003) The stomach and iron deficiency anaemia: A forgotten link. Dig Liver Dis 35:288-295
94. Raja K, Kochhar R, Sethy PK, Dutta U, Bali HK, Varma JS (2004) An endoscopic study of upper-GI mucosal changes in patients with congestive heart failure. Gastrointest Endosc 60:887-893
95. Chodos RB, Wells R Jr, Chaffee WR (1964) A study of ferrokinetics and red cell survival in congestive heart failure. Am J Med 36:553-560
96. Palazzuoli A, Silverberg D, Iovine F, Capobianco S, Giannotti G, Calabro A, Campagna SM, Nuti R (2006) Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. Am Heart J 152(6): 1096.e9-1096.e15
97. van Veldhuisen DJ, Dickstein K, Cohen-Solal A, Lok DJ, Wasserman SM, Baker N, Rosser D, Cleland JG, Ponikowski P (2007) Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia. Eur Heart J 28:2208-2216
98. Ponikowski P, Anker SD, Szachniewicz J, Okonko D, Ledwidge M, Zymlinski R, Ryan E, Wasserman SM, Baker N, Rosser D, Rosen SD, Poole-Wilson PA, Banasiak W, Coats AJ, McDonald K (2007) Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: A randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 49:753-762
99. Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R, Schwartz D, Yachnin T, Steinbruch S, Shapira I, Laniado S, Iaina A (2001) The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: A randomized controlled study. J Am Coll Cardiol 37:1775-1780
100. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085-2098
101. Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A (2006) Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355:2071-2084
102. Phrommintikul A, Haas SJ, Elsik M, Krum H (2007) Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: A meta-analysis. Lancet 369:381-388
103. Danielson BG, Salmonson T, Derendorf H, Geisser P (1996) Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers. Arzneimittelforschung 46:615-621
104. Seligman PA, Dahl NV, Strobos J, Kimko HC, Schleicher RB, Jones M, Ducharme MP (2004) Single-dose pharmacokinetics of sodium ferric gluconate complex in iron-deficient subjects. Pharmacotherapy 24:574-583
105. Van Wyck D, Anderson J, Johnson K (2004) Labile iron in parenteral iron formulations: A quantitative and comparative study. Nephrol Dial Transplant 19:561-565
106. Nissenson AR, Lindsay RM, Swan S, Seligman P, Strobos J (1999) Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial. Am J Kidney Dis 33:471-482
107. Mircescu G, Garneata L, Capusa C, Ursea N (2006) Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients. Nephrol Dial Transplant 21:120-124
108. Agarwal R (2004) Transferrin saturation with intravenous irons: An in vitro study. Kidney Int 66:1139-1144
109. Parkkinen J, von Bonsdorff L, Peltonen S, Gronhagen-Riska C, Rosenlof K (2000) Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration. Nephrol Dial Transplant 15:1827-1834
110. Fishbane S (2003) Safety in iron management. Am J Kidney Dis 41:18-26
111. Agarwal R, Vasavada N, Sachs NG, Chase S (2004) Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 65:2279-2289
112. Agarwal R, Rizkala AR, Kaskas MO, Minasian R, Trout JR (2007) Iron sucrose causes greater proteinuria than ferric gluconate in non-dialysis chronic kidney disease. Kidney Int 72:638-642
113. Attallah N, Osman-Malik Y, Frinak S, Besarab A (2006) Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis 47:644-654
114. Tarng DC, Wei YH, Huang TP, Kuo BI, Yang WC (1999) Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int 55:2477-2486
115. Smith CH, Bidlack WR (1980) Interrelationship of dietary ascorbic acid and iron on the tissue distribution of ascorbic acid, iron and copper in female guinea pigs. J Nutr 110:1398-1408
116. Handelman GJ (2007) Vitamin C neglect in hemodialysis: Sailing between Scylla and Charybdis. Blood Purif 25:58-61
117. Abuelo JG, Schwartz ST, Reginato AJ (1992) Cutaneous oxalosis after long-term hemodialysis. Arch Intern Med 152:1517-1520
118. Canavese C, Petrarulo M, Massarenti P, Berutti S, Fenoglio R, Pauletto D, Lanfranco G, Bergamo D, Sandri L, Marangella M (2005) Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients. Am J Kidney Dis 45:540-549
119. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. New Eng J Med 339:584-590