Pattern of resistance to erythropoietin-stimulating agents in chronic kidney disease

Kidney International

Volumn 80, Issue 5, 2011, Pages 464-474

  Bamgbola, Oluwatoyin F ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Chronic kidney disease; Clinical nephrology; Erythropoietin; Inflammation

Indexed keywords

ALPHA TOCOPHEROL; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIANEMIC AGENT; CONTINUOUS ERYTHROPOIESIS RECEPTOR ACTIVATOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ERYTHROPOIETIN; ERYTHROPOIETIN FC RECEPTOR FUSION PROTEIN; ERYTHROPOIETIN RECEPTOR; FOLIC ACID; GROWTH ARREST SPECIFIC PROTEIN 6; HEAVY METAL; HEMOGLOBIN; IRON; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PEGINESATIDE; PENTOXIFYLLINE; RECOMBINANT ERYTHROPOIETIN; UNCLASSIFIED DRUG; DRUG DERIVATIVE;

AGE DISTRIBUTION; ANEMIA; ASCORBIC ACID DEFICIENCY; BLEEDING; CATHETER INFECTION; CELL BASED GENE THERAPY; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL (TOPIC); DIALYSIS CATHETER; DIET THERAPY; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; ERYTHROCYTOSIS; ERYTHROPOIESIS; EXTRAMEDULLARY HEMATOPOIESIS; FOLATE METABOLISM; FOLIC ACID DEFICIENCY; GRAFT FAILURE; HEMOGLOBIN BLOOD LEVEL; HEMOGLOBINOPATHY; HEMOLYSIS; HEMOLYTIC ANEMIA; HORMONE ACTION; HUMAN; HYPERPARATHYROIDISM; HYPERTENSION; INFLAMMATION; IRON DEFICIENCY; IRON METABOLISM; KIDNEY TRANSPLANTATION; LABORATORY DIAGNOSIS; MESENCHYMAL STEM CELL; MORBIDITY; NONHUMAN; NUTRITIONAL DEFICIENCY; OXIDATIVE STRESS; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; QUALITY OF LIFE; RECEPTOR UPREGULATION; RENAL REPLACEMENT THERAPY; REVIEW; RISK BENEFIT ANALYSIS; SECONDARY HYPERPARATHYROIDISM; SEX DIFFERENCE; TREATMENT RESPONSE; UREMIA; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VITAMIN D DEFICIENCY; CHRONIC KIDNEY FAILURE; DRUG RESISTANCE;

ANEMIA; DRUG RESISTANCE; ERYTHROPOIETIN; HEMATINICS; HUMANS; KIDNEY FAILURE, CHRONIC;

EID: 84857094157     PISSN: 00852538     EISSN: 15231755     Source Type: Journal    
DOI: 10.1038/ki.2011.179     Document Type: Review

References (140)

1. Triolo G. Guidelines for the treatment of anemia in chronic renal failure. G Ital Nefrol 2003; 20(Suppl 24): S61-S82.
2. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). 2004 Annual report.
3. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for anemia in chronic kidney disease. Am J Kidney Dis 2006; 47: S1-S145.
4. Locatelli F, Aljama P, Bárány P et al. Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19(Suppl ii): S1-S47.
5. Port RE, Mehls O. Erythropoietin dosing in children with chronic kidney disease: based on body size or on hemoglobin deficit? Pediatr Nephrol 2009; 24: 435-437.
6. Palmer SC, Navaneethan SD, Craig JC et al. Meta-analysis: erythropoiesisstimulating agents in patients with chronic kidney disease. Ann Intern Med 2010; 153: 23-33.
7. Singh AK, Szczech L, Tang KL et al. Anaemia of CKD-the CHOIR study revisited. Nephrol Dial Transplant 2007; 22: 1806-1810. (Pubitemid 47244743)
8. Singh AK, Szczech L, Tang KL, et al., CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085-2098. (Pubitemid 44749317)
9. Drueke TB, Locatelli F, Clyne N, et al., CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071-2084. (Pubitemid 44749316)
10. Elzen WPJ, Willems JM, Westendorp RGJ et al. Effect of erythropoietin levels on mortality in old age: the Leiden 85-plus Study. CMAJ 2010; 182: 1953-1958.
11. Goodkin DA, Fuller DS, Robinson BM et al. Occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients. J Am Soc Nephrol 2011; 22: 358-365.
12. Greenwood RN, Ronco C, Gastaldon F et al. Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance. Kidney Int 2003; 64: S78-S86. (Pubitemid 37315512)
13. Palis J, Segel GB. Developmental biology of erythropoiesis. Blood Rev 1998; 12: 106-114. (Pubitemid 28327417)
14. Bamgbola OF, Kaskel FJ, Coco M. Analyses of age, gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts. Pediatr Nephrol 2009; 24: 571-579.
15. Shahani S, Braga-Basaria M, Maggio M et al. Androgens and erythropoiesis: past and present. J Endocrinol Invest 2009; 32: 704-716.
16. Biagio RD, Davide S, Natale GD et al. Association of gender and age with erythropoietin resistance in hemodialysis patients: role of menstrual status. Blood Purif 2004; 22: 423-427.
17. Mason-Garcia M, Beckman BS, Brookins JW et al. Development of a new radioimmunoassay for erythropoietin using recombinant erythropoietin. Kidney Int 1990; 38: 969-975. (Pubitemid 20362871)
18. Yuen D, Richardson RM, Fenton SS et al. Quotidian nocturnal hemodialysis improves cytokine profile and enhances erythropoietin responsiveness. ASAIO J 2005; 51: 236-241. (Pubitemid 40677132)
19. Kong QY, Wu X, Li J et al. Loss of phospholipid asymmetry in red blood cells contributes to anemia in uremic patients. Adv Perit Dialysis 2000; 17: 58-60.
20. Bonomini M, Sirolli V, Reale M et al. Involvement of phosphatidylserine exposure in the recognition and phagocytosis of uremic erythrocytes. Am J Kidney Dis 2001; 37: 807-814. (Pubitemid 32268042)
21. Radaeli B. Hydroelectric equilibrium change in dialysis. J Nephrol 2001; 14: S7-S11.
22. Smith EK, Welt LG. The red blood cell as a model for the study of uremic toxins. Arch Intern Med 1970; 126: 827-830.
23. Smogorzewski MJ. Central nervous dysfunction in uremia. Proceedings of the Second International Congress on Uremia Research, Nara, Japan, April 26-28, 2001: Organ Dysfunction in Uremia. Am J Kidney Dis 2001; 38: 580-584.
24. Blaustein MP, Hodgkin AC. The effect of cyanide on the efflux of calcium from squid axon. J Physiol 1969; 200: 497-527.
25. Gallucci MT, Lubrano R, Meloni C et al. Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients. Clin Nephrol 1999; 52: 239-245. (Pubitemid 29467099)
26. Vanella A, Geremia E, Pinturo R et al. Superoxide dismutase activity and reduced glutathione content in erythrocytes of uremic patients on chronic dialysis. Acta Haematol 1983; 70: 312-315. (Pubitemid 13011219)
27. Mendes RAC, Brunini TM, Ellory JC et al. Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure. Cardiovasc Res 2001; 49: 697-712. (Pubitemid 32178373)
28. Dursun E, Ozben T, Süleymanlar G et al. Effect of hemodialysis on the oxidative stress and antioxidants. Clin Chem Lab Med 2002; 40: 1009-1013. (Pubitemid 35356018)
29. Suliman HB, Ali M, Piantadosi CA. Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood 2004; 104: 43-50. (Pubitemid 38879836)
30. Calò LA, Stanic L, Davis PA et al. Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients. Int J Clin Pharmacol Ther 2003; 41: 187-192. (Pubitemid 36603760)
31. Sayan H, Ozacmak VH, Sen F et al. Pharmacological preconditioning with erythropoietin reduces ischemia-reperfusion injury in the small intestine of rats. Life Sci 2009; 84: 364-371.
32. Lahera V, Goicoechea M, de Vinuesa SG et al. Oxidative stress in uremia: the role of anemia correction. J Am Soc Nephrol 2006; 12(Suppl 3): S174-S177. (Pubitemid 44865245)
33. Herrera J, Nava M, Romero F et al. Melatonin prevents oxidative stress resulting from iron and erythropoietin administration. Am J Kidney Dis 2001; 37: 750-757. (Pubitemid 32268036)
34. Stenvinkel P. Inflammatory and atherosclerotic interactions in the depleted uremic patient. Blood Purif 2001; 19: 53-61.
35. Bergström J, Lindholm B, Lacson Jr E et al. What are the causes and consequences of the chronic inflammatory state in chronic dialysis patients? Semin Dial 2000; 13: 163-175.
36. Macdougall IC, Cooper AC. Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant 2002; 17(Suppl 11): S39-S43.
37. Means Jr RT. Recent developments in the anemia of chronic disease. Curr Hematol Rep 2003; 2: 116-121.
38. Nemeth E, Rivera S, Gabayan V et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004; 113: 1271-1276. (Pubitemid 39069926)
39. Lawrence CM, Ray S, Babyonyshev M et al. Crystal structure of the ectodomain of human transferrin receptor. Science 1999; 286: 779-782.
40. Witthuhn BA, Quelle FW, Silvennoinen O et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 1993; 74: 227-236. (Pubitemid 23221699)
41. Klingmüller U, Lorenz U, Cantley LC et al. Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell 1995; 80: 729-738.
42. Akagi S, Ichikawa H, Okada T et al. The critical role of SRC homology domain 2-containing tyrosine phosphatase-1 in recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis patients. J Am Soc Nephrol 2004; 15: 3215-3224. (Pubitemid 39578854)
43. Silva M, Grillot D, Benito A et al. Erythropoietin can promote erythroid progenitor survival by repressing apoptosis through Bcl-XL and Bcl-2. Blood 1996; 88: 1576-1582. (Pubitemid 26307051)
44. Kashii Y, Uchida M, Kirito K et al. A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction. Blood 2000; 96: 941-949. (Pubitemid 30616858)
45. Matsumoto A, Masuhara M, Mitsui K et al. CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. Blood 1997; 9: 3148-3154.
46. Peltola KJ, Paukku K, Aho TL et al. Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3. Blood 2004; 103: 3744-3750. (Pubitemid 38596290)
47. La Ferla K, Reimann C, Jelkmann W et al. Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. FASEB J 2002; 16: 1811-1813.
48. Beltrán S, Gavela E, Kanter J et al. Beginning hemodialysis: do patients with a failed renal transplant start in worse condition? Transplant Proc 2009; 41: 2129-2131.
49. Ayus JC, Achinger SG. At the peril of dialysis patients: ignoring the failed transplant. Semin Dialysis 2005; 18: 180-184. (Pubitemid 40847274)
50. Goicoechea M, Caramelo C, Rodriguez P et al. Role of type of vascular access in erythropoietin and intravenous iron requirements in haemodialysis. Nephrol Dial Transplant 2001; 16: 2188-2193. (Pubitemid 33062142)
51. Goldstein SL, Ikizler TP, Zappitelli M et al. Non-infected hemodialysis catheters are associated with increased inflammation compared to arteriovenous fistulas: non-infected catheters increase CRP. Kidney Int 2009; 76: 1063-1069.
52. Wystrychowski G, Kitzler TM, Thijssen S et al. Impact of switch of vascular access type on key clinical and laboratory parameters in chronic haemodialysis patients. Nephrol Dial Transplant 2009; 24: 2194-2200.
53. Yuen D, Richardson RM, Fenton SS et al. Quotidian nocturnal hemodialysis improves cytokine profile and enhances erythropoietin responsiveness. ASAIO J 2005; 51: 236-241. (Pubitemid 40677132)
54. Eschach JW, Cook JD, Scribner BH et al. Iron balance in hemodialysis patients. Ann Intern Med 1977; 87: 710.
55. Kalantar-Zadeh K, Hoffken B, Wunsch H et al. Diagnosis of iron deficiency anemia in renal failure patients during the post-eythropoeitin era. Am J Kidney Dis 1995; 26: 292.
56. Hershko C, Hoffbrand AV, Keret D et al. Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. Haematologica 2005; 90: 585.
57. Fishbane S, Frei GL, Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis 1995; 26: 41-46.
58. Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 2006; 1(Suppl 1): S4-S8.
59. Tonelli M, Winkelmayer WC, Jindal KK et al. The cost-effectiveness of maintaining higher hemoglobin targets with erythropoietin in hemodialysis patients. Kidney Int 2003; 64: 295-304. (Pubitemid 36714184)
60. Brugnara C. Iron deficiency and erythropoiesis: new diagnostic approaches. Clin Chem 2003; 49: 1573-1578. (Pubitemid 37194211)
61. Gallieni M, Corsi C, Brancaccio D. Hyperparathyroidism and anemia in renal failure. Am J Nephrol 2000; 20: 89-96. (Pubitemid 30224017)
62. Al-Hilali N, Al-Humoud H, Ninan VT et al. Does parathyroid hormone affect erythropoietin therapy in dialysis patients? Med Princ Pract 2007; 16: 63-67. (Pubitemid 44924460)
63. Trunzo JA, McHenry CR, Schulak JA et al. Effect of parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism. Surgery 2008; 144: 915-918.
64. Meytes D, Shacked N, Blum M et al. Effect of excess parathyroid hormone on human bone marrow fibroblasts. Nephron 1990; 55: 6-9. (Pubitemid 20135094)
65. Brunner S, Theiss HD, Murr A et al. Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells. Am J Physiol Endocrinol Metab 2007; 293: E1670-E1675. (Pubitemid 350255118)
66. Duarte ME, Carvalho EF, Cruz EA et al. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy. Braz J Med Biol Res 2002; 35: 25-29. (Pubitemid 34183198)
67. Diskin CJ, Stokes TJ, Dansby LM et al. Can acidosis and hyperphosphataemia result in increased erythropoietin dosing in haemodialysis patients? Nephrology (Carlton) 2006; 11: 394-399. (Pubitemid 44470086)
68. González EA, Lund RJ, Martin KJ et al. Treatment of a murine model of high-turnover renal osteodystrophy by exogenous BMP-7. Kidney Int 2002; 61: 1322-1331. (Pubitemid 34304493)
69. Holick MF. Vitamin D and the kidney. Kidney Int 1987; 32: 912-929. (Pubitemid 18015525)
70. Coburn JW, Koppel MH, Brickman AS et al. Study of intestinal absorption of calcium in patients with renal failure. Kidney Int 1973; 3: 264-272.
71. Koenig KG, Lindberg JS, Zerwekh JE et al. Free and total 1, 25-dihydroxyvitamin D levels in subjects with renal disease. Kidney Int 1992; 41: 161-165.
72. Langman CB, Brooks ER. Renal osteodystrophy in children: a systemic disease associated with cardiovascular manifestations. Growth Horm IGF Res 2006; 16: S79-S83.
73. Aucella F, Gatta G, Vigilante M et al. Increased in vitro and ex vivo proliferation of erythroid precursors induced by calcitriol in chronic renal failure. Synergistic effect with rHuEPO. G Ital Nefrol 2002; 19: 137-142.
74. Sezer S, Tutal E, Bilgic A et al. Possible influence of vitamin D receptor gene polymorphisms on recombinant human erythropoietin requirements in dialysis patients. Transplant Proc 2007; 39: 40-44. (Pubitemid 46175972)
75. Ertürk S, Kutlay S, Karabulut HG et al. The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients. Am J Kidney Dis 2002; 40: 816-823.
76. Garbossa G, Gutnisky A, Nesse A. The inhibitory action of aluminum on mouse bone marrow cell growth: evidence for an erythropoietin-and transferrin-mediated mechanism. Miner Electrolyte Metab 1994; 20: 141-146. (Pubitemid 24300593)
77. Saper RB, Phillips RS, Sehgal A et al. Lead, mercury, and arsenic in US-and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA 2008; 300: 915-923.
78. Javier III FC, McCormick DP, Alcock NW. Lead screening among low-income children in Galveston, Texas. Clin Pediatr (Phila) 1999; 38: 655-660.
79. Peraza MA, Ayala-Fierro F, Barber DS et al. Effects of micronutrients on metal toxicity. Environ Health Perspect 1998; 106: 203-216. (Pubitemid 28196045)
80. Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol 2009; 16: 187-194.
81. Tarng DC, Chang JG, Huang TP. Resistance to recombinant erythropoietin in a hemodialysis patient with heterozygous hemoglobinopathy J-Meinung. Am J Kidney Dis 1997; 29: 769-772.
82. Michlitsch J, Azimi M, Hoppe C et al. Newborn screening for hemoglobinopathies in California. Pediatr Blood Cancer 2009; 52: 486-490.
83. Modell B, Khan M, Darlison M et al. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008; 10: 42.
84. Wong WY, Elliott-Mills D, Powars D. Renal failure in sickle cell anemia. Hematol Oncol Clin North Am 1996; 10: 1321-1331. (Pubitemid 26412253)
85. Di Iorio B, Guastaferro P, Bellizzi V. Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor. Blood Purif 2003; 21: 376-380. (Pubitemid 37346711)
86. Irwing JJ, Kirchner JT. Anemia in children. Am Fam Physician 2001; 61: 1379-1386. (Pubitemid 32983374)
87. Budman DR, Steinberg AD. Hematologic aspects of systemic lupus erythematosus: current concepts. Ann Intern Med 1977; 86: 220-229. (Pubitemid 8042804)
88. Sultan SM, Begum S, Isenberg DA. Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Rheumatology (Oxford) 2003; 42: 230-234. (Pubitemid 36305607)
89. Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore) 2006; 85: 147-156. (Pubitemid 43833013)
90. Rugginenti P. Post-transplant hemolytic-uremic syndrome. Kidney Int 2002; 62: 1093-1104.
91. Sharples EJ, Varagunam M, Sinnott PJ et al. The effect of proinflammatory cytokine gene and angiotensin-converting enzyme polymorphisms on erythropoietin requirements in patients on continuous ambulatory peritoneal dialysis. Perit Dial Int 2006; 26: 64-68. (Pubitemid 44339663)
92. Jeong KH, Lee TW, Ihm CG et al. Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis. Exp Mol Med 2008; 40: 161-166.
93. Le Meur Y, Lorgeot V, Comte L et al. Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements. Am J Kidney Dis 2001; 38: 510-517. (Pubitemid 32803061)
94. Mohanram A, Zhang Z, Shahinfar S et al. The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. Kidney Int 2008; 73: 630-636. (Pubitemid 351264116)
95. Messa P, Nicolini MA, Cesana B et al. Efficacy prospective study of different frequencies of Epo administration by i.v. and s.c. routes in renal replacement therapy patients. Nephrol Dial Transplant 2006; 21: 431-436. (Pubitemid 43159999)
96. Pizzarelli F, David S, Sala P et al. Iron-replete hemodialysis patients do not require higher EPO dosages when converting from subcutaneous to intravenous administration: results of the Italian Study on Erythropoietin Converting (ISEC). Am J Kidney Dis 2006; 47: 1027-1035. (Pubitemid 43767329)
97. Bamgbola OF, Kaskel F. Role of folate deficiency on erythropoietin resistance in pediatric and adolescent patients on chronic dialysis. Pediatr Nephrol 2005; 20: 1622-1629. (Pubitemid 41554477)
98. Boeschoten EW, Schrijver J, Krediet RT et al. Deficiencies of vitamins in CAPD patients: the effect of supplementation. Nephrol Dial Transplant 1988; 3: 187-193.
99. Phekoo K, Williams Y, Schey SA et al. Folate assays: serum or red cell? J Royal Coll Physicians London 1979; 31: 291-295.
100. Hershko C, Grossowicz N, Rachmilewitz M et al. Serum and erythrocyte folates in combined iron and folate deficiency. Am J Clin Nutrition 1975; 28: 1217-1222.
101. Paine CJ, Hargrove Jr MD, Eichner ER. Folic acid binding protein and folate balance in uremia. Archives Int Med 1976; 136: 756-760.
102. Leblanc M, Pichette V, Geadahy D et al. Folic acid and pyridoxal-50-phosphate losses during high-efficiency hemodialysis in patients without hydrosoluble vitamin supplementation. J Ren Nutr 2000; 10: 196-201.
103. Lasseur C, Parrot F, Delmas Y et al. Impact of high-flux/high-efficiency dialysis on folate and homocysteine metabolism. J Nephrol 2001; 14: 32-35. (Pubitemid 32201247)
104. Bamonti-Catena F, Buccianti G, Porcella A et al. Folate measurements in patients on regular hemodialysis treatment. Am J Kidney Dis 1999; 33: 492-497. (Pubitemid 29107026)
105. Koury MJ, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr 2004; 24: 105-131. (Pubitemid 38938788)
106. Fort J. Chronic renal failure: a cardiovascular risk factor. Kidney Int Suppl 2005; 68(Suppl 99): S25-S29.
107. Jacobs C. Intravenous vitamin C can improve anemia in erythropoietinhyporesponsive hemodialysis patients. Nat Clin Pract Nephrol 2006; 2: 552-553. (Pubitemid 44465673)
108. Singer R, Rhodes HC, Chin G et al. High prevalence of ascorbate deficiency in an Australian peritoneal dialysis population. Nephrology (Carlton) 2008; 13: 17-22.
109. Delanghe JR, Langlois MR, De Buyzere ML et al. Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clin Chem 2007; 53: 1397-1400. (Pubitemid 47206335)
110. Horio F, Kiyama K, Kobayashi M et al. Ascorbic acid deficiency stimulates hepatic expression of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1, in scurvy-prone ODS rats. J Nutr Sci Vitaminol (Tokyo) 2006; 52: 28-32.
111. Guery MJ, Douillard C, Marcelli-Tourvieille S et al. Doctor, my son is so tiredy about a case of hereditary fructose intolerance. Ann Endocrinol (Paris) 2007; 68: 456-459.
112. Akikusa JD, Garrick D, Nash MC. Scurvy: forgotten but not gone. J Paediatr Child Health 2003; 39: 75-77. (Pubitemid 36238140)
113. Giancaspro V, Nuzziello M, Pallotta G et al. Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial. J Nephrol 2000; 13: 444-449. (Pubitemid 32015746)
114. Sakaguchi M, Maeda Y, Naiki Y et al. Possible role of soluble erythropoietin receptors in renal anemia. Nippon Jinzo Gakkai Shi 2002; 44: 524-529. (Pubitemid 35408466)
115. Cournoyer D, Toffelmire EB, Wells GA et al. Anti-erythropoietin antibodymediated pure red cell aplasia after treatment with recombinant erythropoietin products: recommendations for minimization of risk. J Am Soc Nephrol 2004; 15: 2728-2734. (Pubitemid 41103380)
116. Rossert J, Casadevall N, Eckardt KU. Anti-erythropoietin antibodies and pure red cell aplasia. J Am Soc Nephrol 2004; 15: 398-406. (Pubitemid 38140780)
117. Weber G, Gross J, Kromminga A et al. Allergic skin and systemic reactions in a patient with pure red cell aplasia and anti-erythropoietin antibodies challenged with different epoetins. J Am Soc Nephrol 2002; 13: 2381-2383. (Pubitemid 34925249)
118. Asari A, Gokal R. Pure red cell aplasia secondary to epoetin alpha responding to darbepoetin alpha in a patient on peritoneal dialysis. J Am Soc Nephrol 2004; 15: 2204-2207. (Pubitemid 39031359)
119. Boven K, Stryker S, Knight J et al. The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes. Kidney Int 2005; 67: 2346-2353. (Pubitemid 41623396)
120. Eckardt KU, Casadevall N. Pure red-cell aplasia due to anti-erythropoietin antibodies. Nephrol Dial Transplant 2003; 18: 865-869. (Pubitemid 36592522)
121. Casadevall N, Nataf J, Viron B et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002; 346: 469-475. (Pubitemid 34441737)
122. Eiselt J, Racek J, Trefil L et al. Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients. Artif Organs 2001; 25: 430-436. (Pubitemid 32868563)
123. Németh I, Túri S, Haszon I et al. Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis. Pediatr Nephrol 2000; 14: 13-17. (Pubitemid 30085335)
124. Johnson DW, Hawley CM, Rosser B et al. Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial. BMC Nephrol 2008; 9: 8.
125. Robertson FM, Ross MS, Tober KL et al. Inhibition of pro-inflammatory cytokine gene expression and papilloma growth during murine multistage carcinogenesis by pentoxifylline. Carcinogenesis 1996; 17: 1719-1728. (Pubitemid 26280398)
126. Chiang CK, Yang SY, Peng YS et al. Atorvastatin increases erythropoietinstimulating agent hyporesponsiveness in maintenance hemodialysis patients: role of anti-inflammation effects. Am J Nephrol 2009; 29: 392-397.
127. Chang JW, Lee EK, Kim TH et al. Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on HD: a pilot study. Am J Nephrol 2007; 27: 70-74. (Pubitemid 46364543)
128. Calò LA, Davis PA, Pagnin E et al. Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1: studies in humans and in an animal model. Nephrol Dial Transplant 2008; 23: 890-895. (Pubitemid 351767567)
129. Aoun B, Bérard E, Vitkevic R et al. L-carnitine supplementation and EPO requirement in children on chronic hemodialysis. Pediatr Nephrol 2010; 25: 557-560.
130. Guarnieri G, Biolo G, Vinci P et al. Advances in carnitine in chronic uremia. J Ren Nutr 2007; 17: 23-29. (Pubitemid 46014452)
131. Bellinghieri G, Santoro D, Calvani M et al. Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients. J Ren Nutr 2005; 15: 13-17. (Pubitemid 40093676)
132. Macdougall IC. Novel erythropoiesis-stimulating agents: a new era in anemia management. Clin J Am Soc Nephrol 2008; 3: 200-207.
133. Hedenus M, Vansteenkiste J, Kotasek D et al. Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebocontrolled trials. J Clin Oncol 2005; 23: 6941-6948.
134. Schriebl K, Trummer E, Lattenmayer C et al. Biochemical characterization of rhEpo-Fc fusion protein expressed in CHO cells. Protein Expr Purif 2006; 49: 265-275. (Pubitemid 44416228)
135. Jaakkola P, Mole DR, Tian Y et al. Targeting of HIF-a to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001; 292: 468-472. (Pubitemid 32335942)
136. Angelillo-Scherrer A, Burnier L, Lambrechts D et al. Role of Gas6 in erythropoiesis and anemia in mice. J Clin Invest 2008; 118: 583-596. (Pubitemid 351206548)
137. Ghinassi B, Verrucci M, Jelicic K et al. Interleukin-3 and erythropoietin cooperate in the regulation of the expression of erythroid-specific transcription factors during erythroid differentiation. Exp Hematol 2007; 35: 735-747. (Pubitemid 46601755)
138. Wang LN, Liu K, Lee D et al. Comparison of drug and cell-based deliveryengineering adult mesenchymal stem cells to deliver human Erythropoietin. Gene Ther Mol Biol 2009; 13: 321-330.
139. Binley Z, Askham S, Iqball H et al. Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy. Blood 2002; 100: 2406-2413.
140. Schaffer DV, Koerber JT, Lim K. Molecular engineering of viral gene delivery vehicles. Annu Rev Biomed Eng 2008; 10: 169-194.