Erythropoiesis stimulatory agent- resistant anemia in dialysis patients: Review of causes and management

Blood Purification

Volumn 29, Issue 1, 2010, Pages 1-12

  Kanbay, Mehmet ^a   Perazella, Mark A ^c   Kasapoglu, Benan ^b   Koroglu, Mustafa ^b   Covic, Adrian ^d  

^a Section of Nephrology   (Turkey)

^b FATIH UNIVERSITY MEDICAL SCHOOL   (Turkey)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d C I PARHON NATIONAL INSTITUTE OF ENDOCRINOLOGY   (Romania)

Author keywords

Anemia; Chronic kidney disease; Darbepoetin; Erythropoiesis stimulatory agent resistance; Erythropoietin; Inflammation; Iron deficiency

Indexed keywords

ALPHA TOCOPHEROL; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIANEMIC AGENT; ASCORBIC ACID; C REACTIVE PROTEIN; CARNITINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FLUINDOSTATIN; HEMOGLOBIN; HEPCIDIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 1; INTERLEUKIN 6; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PENTOXIFYLLINE; RECOMBINANT ERYTHROPOIETIN; SHI QUAN DA BU TANG; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA;

ANEMIA; CARNITINE DEFICIENCY; CHRONIC KIDNEY DISEASE; DRUG DOSE TITRATION; DRUG MEGADOSE; HEMODIAFILTRATION; HEMODIALYSIS; HEMODIALYSIS PATIENT; HUMAN; HYPERPARATHYROIDISM; INFLAMMATION; LOW DRUG DOSE; MALNUTRITION; MYELOPROLIFERATIVE DISORDER; NONHUMAN; OCCULT CANCER; PATIENT CARE; PRIORITY JOURNAL; PURE RED CELL ANEMIA; REVIEW; TREATMENT INDICATION; TREATMENT OUTCOME; CHRONIC KIDNEY FAILURE; DRUG RESISTANCE; ERYTHROPOIESIS; IRON DEFICIENCY ANEMIA; PATIENT COMPLIANCE; PHYSIOLOGY; RENAL REPLACEMENT THERAPY;

ANEMIA; ANEMIA, IRON-DEFICIENCY; DRUG RESISTANCE; ERYTHROPOIESIS; ERYTHROPOIETIN, RECOMBINANT; HEMATINICS; HUMANS; INFLAMMATION; KIDNEY FAILURE, CHRONIC; PATIENT COMPLIANCE; RENAL DIALYSIS;

EID: 70349836253     PISSN: 02535068     EISSN: None     Source Type: Journal    
DOI: 10.1159/000245041     Document Type: Review

References (98)

1. World Health Organization: Nutritional Anaemias: Report of a WHO Scientific Group. Geneva, World Health Organization, 1968.
2. Kazmi WH, Kausz AT, Khan S, Abichandani R, Ruthazer R, Obrador GT, Pereira BJ: Anemia: an early complication of chronic renal insuff iciency. Am J Kidney Dis 2001;38:803-812.
3. Nurko S: Anemia in chronic kidney disease: causes, diagnosis, treatment. Cleve Clin J Med 2006;73:289-297.
4. Berns JS: Should the target hemoglobin for patients with chronic kidney disease treated with erythropoietic replacement therapy be changed? Semin Dial 2005;18:22-29.
5. Portolés J, López-Gómez JM, Aljama P, MAR Study Group: A prospective multicentre study of the role of anaemia as a risk factor in haemodialysis patients: the MAR Study. Nephrol Dial Transplant 2007; 22:500-507.
6. Locatelli F, Covic A, Eckardt KU, Wiecek A, Vanholder R, ERA-EDTA ERBP Advisory Board: Anaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP). Nephrol Dia l Tra nsplant 2009;24:348-354.
7. Pisoni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, Bommer J, Cruz JM, Kerr PG, Mendelssohn DC, Held PJ, Port FK: Anaemia management and outcome from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2004; 44:94-111.
8. Priyadarshi A, Shapiro JI: Erythropoietin resistance in the treatment of the anemia of chronic renal failure. Semin Dial 2006;19:273-278.
9. Kilpatrick RD, Critchlow CW, Fishbane S, Besarab A, Stehman-Breen C, Krishnan M, Bradbury BD: Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3:1077-1083.
10. Szczech LA, Barnhart HX, Inrig JK, Reddan DN, Sapp S, Califf RM, Patel UD, Singh AK: Secondary analysis of the CHOIR trial epo-etin-alpha dose and achieved hemoglobin outcomes. Kidney Int 2008; 74:791-798.
11. National Kidney Foundation: NKF-DOQI Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure. New York, National Kidney Foundation, 2006.
12. Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt KU, Hörl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S, European Best Practice Guidelines Working Group: Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19(suppl 2):ii1-ii47.
13. Eknoyan G, Latos DL, Lindberg J: Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis 2003; 41:868-876.
14. Drueke T: Hyporesponsiveness to recombi-nant human erythropoietin. Nephrol Dial Transplant 2001; 16:25-28.
15. Smrzova J, Balla J, Bárány P: Inflammation and resistance to erythopoiesis-stimulating agents-what do we know and what needs to be clarified? Nephrol Dial Transplant 2005; 20:2-7.
16. Lacombe C: Resistance to erythropoietin. N Engl J Med 1996;334:660-662.
17. Al-Hilali N, Al-Humoud H, Ninan VT, Nampoory MR, Puliyclil MA, Johny KV: Does parathyroid hormone affect erythro-poietin therapy in dialysis patients? Med Princ Pract 2007;16:63-67.
18. Kaynar K, Ozkan G, Erem C, Gul S, Yilmaz M, Sonmez B, Ozdemir F, Ulusoy S: An unusual etiology of erythropoietin resistance: hy per thy roidism. Ren Fail 2007;29:759-761.
19. Costa E, Lima M, Alves JM, Rocha S, Rocha-Pereira P, Castro E, Miranda V, do SF, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: Inflammation, T-cell phenotype, and inflammatory cytokines in chronic kidney disease patients under hemodialysis and its relationship to resistance to recombinant human erythropoietin therapy. J Clin Immunol 2008;28:268-275.
20. Maury CP, Liljestrom M, Laiho K, Tiitinen S, Kaarela K, Hurme M: Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18. J Intern Med 2004;256:145-152
21. Jeong KH, Lee TW, Ihm CG, Lee SH, Moon JY: 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.
22. Cooper AC, Mikhail A, Lethbridge MW, Ke-meny DM, Macdougall IC: 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 2003;14:1776-1784.
23. Pecoits-Filho R, Heimburger O, Barany P, Suliman M, Fehrman-Ekholm I, Lindholm B, Stenvinkel P: Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003; 41:1212-1218.
24. Panichi V, Mig liori M, De Pietro S, et al: Plasma C-reactive protein in hemodialysis patients: a cross-sectional, longitudinal clinica l sur vey. Blood Purif 2000;18:30-36.
25. Del Vecchio L, Pozzoni P, Andrulli S, Locatelli F: Inflammation and resistance to treatment with recombinant human erythropoietin. J Ren Nutr 2005;15:137-141.
26. Shinzato T, Abe K, Furusu A, Harada T, Shinzato K, Miyazaki M, Kohno S: Serum pro-hepcidin level and iron homeostasis in Japanese dialysis patients with erythropoie-tin (EPO)-resistant anemia. Med Sci Monit 2008;14:431-437.
27. Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD: Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis 2003; 42:761-773.
28. Costa E, Rocha S, Rocha-Pereira P, Nascimento H, Castro E, Miranda V, Faria Mdo S, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients Am J Nephrol 2008;28:935-940.
29. Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-788.
30. Nemeth E, Rivera S, Gabayan V, et al: IL-6 mediates hypoferremia of in-flammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest, 2004;113:1271-1276.
31. Nicolas G, Chauvet C, Viatte L, et al: The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002;110:1037-1044
32. Lee P, Peng H, Gelbart T, Wang L, Beutler E: Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005; 102:1906-1910.
33. Kartsios EC, Liakopoulos V, et al: Does hepcidin affect erythropoiesis in hemodialysis patients? Acta Haematol 2006; 116:238-244.
34. Atanasiu V, Manolescu B, Stoian I: Hepcidin the link between inflammation and anemia in chronic renal failure, Rom. J Intern Med 2006; 44:25-33.
35. Sela BA: Hepcidin: the discovery of a small protein with a pivotal role in iron homeostasis. Harefuah 2008;147:261-266.
36. van der Putten K, Braam B, Jie KE, Gaillard CA: Mechanisms of disease: erythropoietin resistance in patients with both heart and kidney failure. Nat Clin Pract Nephrol 2008;4:47-57.
37. Malyszko J, Malyszko JS, Hryszko T, Pawlak K, Mysliwiec M: Is hepcidin a link between anemia, inflammation and liver function in hemodialyzed patients? Am J Nephrol 2005;25:586-590.
38. Costa E, Pereira BJ, Rocha-Pereira P, Rocha S, Reis F, Castro E, Tei xeira F, Miranda V, do Sameiro Faria M, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: Role of prohepcidin, inflammatory markers and iron status in resistance to rhEPO therapy in hemodialysis patients. Am J Nephrol 2008;28:677-683.
39. Kato A, Tsuji T, Luo J, Sakao Y, Yasuda H, Hishida A: Association of prohepcidin and hepcidin-25 with erythropoietin response and ferritin in hemodialysis patients. Am J Nephrol 2008; 28:115-121.
40. Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT: Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997; 100:2310-2314.
41. Azizi M, Rousseau A, Eza n E, et al: Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest 1996; 97:839-844.
42. Kwack C, Balakrishnan VS: Managing erythropoietin hyporesponsiveness. Semin Dial 2006;19:146-151.
43. Qureshi IZ, Abid K, Ambreen F, Qureshi AL: Angiotensin converting enzyme inhibitors impair recombinant human erythropoietin induced erythropoiesis in patients with chronic renal failure. Saudi Med J 2007;28:193-196.
44. Sharples EJ, Varagunam M, Sinnott PJ, Mc-Closkey DJ, Raftery MJ, Yaqoob MM: 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.
45. Saudan P, Halabi G, Perneger T, Wasserfall-en JB, Wauters JP, Martin PY, Western Switzerland Dialysis Group: ACE inhibitors or angiotensin II receptor blockers in dialysed patients and erythropoietin resistance. J Nephrol 2006; 19:91-96.
46. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD: Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003;63:793-808.
47. Di Iorio B, Cirillo M, Bellizzi V, Stellato D, De Santo NG: Prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients - the Campania Dialysis Registr y. Int J Artif Organs 2007;30:325-333.
48. Hauner H: Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc 2005;64:163-169.
49. Axelsson J, Qureshi AR, Heimburger O, Li nd hol m B, Stenvi n kel P, Bara ny P: Body fat mass and serum leptin levels influence epoetin sensitivity in patients with ESRD. Am J Kidney Dis 2005;46:628-634
50. Kotanko P, Thijssen S, Levin NW: Association between erythropoietin responsiveness and body composition in dialysis patients. Blood Purif 2008; 26:82-89.
51. Lin CL, Hung CC, Yang CT, Huang CC: Improved anemia and reduced erythropoietin need by medical or surgical intervention of secondary hyperparathyroidism in hemodialysis patients. Ren Fail 2004; 26:289-295.
52. Stoffel MP, Haverkamp H, Kromminga A, Lauterbach KW, Baldamus CA: Prevalence of anti-erythropoietin antibodies in hemodialysis patients without clinical signs of pure red cell aplasia: comparison between hypo- and normoresponsive patients treated with epoetins for renal anemia. Nephron Clin Pract 2007;105:90-98.
53. Kharagjitsingh AV, Korevaar JC, Vandenbroucke JP, Boeschoten EW, Krediet RT, Daha MR, Dekker FW, NECOSAD Study Group: Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated antibodies, and pure red cell aplasia in dialysis patients. Kidney Int 2005; 68:1215-1222.
54. Movilli E, Cancarini GC, Zani R, Camerini C, Sandrini M, Maiorca R: Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from the use of biocompatible membranes in haemodial-ysis patients. Nephrol Dial Transplant 2001;16:111-114.
55. Movilli E, Cancarini GC, Vizzardi V, Camerini C, Brunori G, Cassamali S, Maiorca R: Epoetin requirement does not depend on dialysis dose when Kt/N >1.33 in patients on regular dialysis treatment with cellulosic membranes and adequate iron stores. J Nephrol 2003;16:546-551.
56. K ita mu ra Y, Satoh K, Satoh T, Ta k ita M, Matsuura A: Effect of L-carnitine on erythroid colony formation in Mouse bone marrow cells. Nephrol Dial Transplant 2005;20:981-984.
57. Locatelli F, Canaud B, Eckardt K, et al: Oxidative stress in endstage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272-1280.
58. Cairo G, Castrusini E, Minotti G, et al: Superoxide and hydrogen peroxide-dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury. FASEB J 1996; 10:1326-1335.
59. Reuter SE, Evans AM, Faull RJ, et al: Impact of haemodialysis on individual endogenous plasma acylcarnitine concentrations in end-stage renal disease. Ann Clin Biochem 2005; 42:387-393.
60. Reuter SE, Faull RJ, Ranieri E, Evans AM: Endogenous plasma carnitine pool composition and response to erythropoietin treatment in chronic haemodialysis patients. Nephrol Dial Transplant 2009;24:990-996.
61. Caillette A, Barreto S, Gimenez E, Labeeuw M, Zech P: Is erythropoietin treatment safe and effective in myeloma patients receiving hemodialysis? Clin Nephrol 1993;40:176-178.
62. Maisnar V, Chroust K: Treatment of associated anemia in different hematological disorders with epoetin alpha. Neoplasma 2004;51:379-384.
63. Costa E, Rocha S, Rocha-Pereira P, Castro E, Miranda V, do Sameiro Faria M, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: Altered erythrocyte membrane protein composition in chronic kidney disease stage 5 patients under haemodialysis and recombi-nant human erythropoietin therapy. Ren Fail. 2008;30:971-975.
64. Valenti L, Valenti G, Como G, Santorelli G, Dongiovanni P, Rametta R, Fracanzani AL, Tavazzi D, Messa PG, Fargion S: HFE genotype influences erythropoiesis support requirement in hemodialysis patients: a prospective study. Am J Nephrol 2008;28:311-316.
65. Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC: Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 1997;16:383-386.
66. Costa E, Rocha S, Rocha-Pereira P, Reis F, Castro E, Teixeira F, Miranda V, do Sameiro Faria M, Loureiro A, Quintanilha A, Belo L, Santos-Silva A: DMT1 (NRAMP2/DCT1) genetic variability and resistance to recombinant human erythropoietin therapy in chronic kidney disease patients under haemodialysis. Acta Haematol 2008;120:11-13.
67. Chang PM, Ng YY: Amiodarone-induced hypothyroidism with EPO-resistant anemia in a patient with chronic renal failure. J Chin Med Assoc 2008;71:576-578.
68. K aw a no Y, Ta k aue Y, Kuroda Y, Mi n kuc h i J, Kawashima S: Effect on alleviation of renal anemia by haemodialysis using the highflux dialyzer (BK-F). Kidney Dial 1994;34:200-203.
69. Ayli D, Ayli M, Azak A, Yüksel C, Kosmaz GP, Atilgan G, Dede F, Abayli E, Camlibel M: The effect of high-flux hemodialysis on renal anemia. J Nephrol 2004;17:701-706.
70. Locatelli F, Andrulli S, Pecchini F, et al: Effect of high-flux dialysis on the anaemia of haemodialysis patients. Nephrol Dial Transplant 2000;15:1399-1409.
71. Yokoyama H, Kawaguchi T, Wada T, Takahashi Y, Higashi T, Yamazaki S, Fukuhara S, Akiba T, Akizawa T, Asano Y, Kurokawa K, Saito A, J-DOPPS Research Group: Biocom-patibility and permeability of dialyzer membranes do not affect anemia, erythropoietin dosage or mortality in japanese patients on chronic non-reuse hemodialysis: a prospective cohort study from the J-DOPPS II study. Nephron Clin Pract 2008; 109:100-108.
72. Molina M, Navarro MJ, Palacios ME, de Gracia MC, García Hernández MA, Ríos Moreno F, Pérez Silva FM: Importance of ultrapure dialysis liquid in response to the treatment of renal anaemia with darbepoetin in patients receiving haemodialysis. Nefrologia 2007;27:196-201.
73. Ballabeni C, Maccario M, Ciurlino D, Martino S, Tentori F, Bigatti G, Bertoli SV: Online hemodiafiltration with endogenous reinfusion (HFR). Experience of a Centre. G Ital Nefrol 2004; (suppl 30):181-184.
74. Jirka T, Cesare S, Di Benedetto A, Perera Chang M, Ponce P, Richards N, Tetta C, Vaslaky L: Mortality risk for patients receiving hemodiafiltration versus hemodialysis. Kidney Int 2006;70:1524.
75. Keven K, Kutlay S, Nergizoglu G, Ertürk S: Randomized, crossover study of the effect of vitamin C on EPO response in hemodialysis patients. Am J Kidney Dis 2003;41:1233-1239.
76. Tarng DC, Hung SC, Huang TP: Effect of intravenous ascorbic acid medication on serum levels of soluble transferrin receptor in haemodialysis patients. J Am Soc Nephrol 2004;15:2486-2493.
77. Attallah N, Osman-Malik Y, Frinak S, Besarab A: Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hypore-sponsive anemia and hyperferritinemia. Am J Kidney Dis 2006;47:644-654.
78. Shahrbanoo K, Taziki O: Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hyperferritinemia. Saudi J Kidney Dis Transpl 2008;19:933-936.
79. Taji Y, Morimoto T, Okada K, Fukuhara S, Fukui T, Kuwahara T: Effect of intravenous ascorbic acid on erythropoiesis and quality of life in unselected hemodialysis patients. J Nephrology 2004; 17:537-543.
80. Biesalski HK: Parenteral ascorbic acid in haemodialysis patients. Curr Opin Clin Nutr Metab Care 2008;11:741-746.
81. Canavese C, Marangella M, Stratta P: Think of oxalate when using ascorbate supplementation to optimize iron therapy in dialysis patients. Nephrol Dial Transplant 2008;23:1463-1464.
82. Winklhofer-Roob BM, Rock E, Ribalta J, Shmerling DH, Roob JM: Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies. Mol Aspects Med 2003; 24:391-402.
83. Cristol JP, Bosc J Y, Badiou S, et al: Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transplant 1997; 12:2312-2317.
84. Gogu SR, Lertora JJ, George WJ, Hyslop NE, Agrawal KC: Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E. Exp Hematol 1991; 19:649-652.
85. Cruz DN, De Cal M, Garzotto F, Brendolan A, Nalesso D, Corradi V, Ronco C: Effect of vitamin E-coated dialysis membranes on anemia in patients with chronic kidney disease: an Italian multicenter study. Int J Artif Organs 2008; 31:545-552.
86. Hurot JM, Cucherat M, Haugh M, et al: Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002;13:708-714.
87. Di Iorio BR, Guastaferro P, Cillo N, Cucciniello E, Bellizzi V. Effect of L-carnitine administration on erythropoietin use in thalassemic minor haemodialysis patients. Nephrol Dial Transplant 2007;22: 954-955.
88. Kadiroglu AK, Yilmaz ME, Sit D, Kara IH, Isikoglu B: The evaluation of postdialysis Lcarnitine administration and its effect on weekly requiring doses of rHuEPO in hemo-dia lysis patients. Ren Fail 2005;27:367-372.
89. Calò LA, Davis PA, Pagnin E, Bertipaglia L, Naso A, Piccoli A, Corradini R, Spinello M, Savica V, Dalla Libera L: Car nitine-med iated 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.
90. Sirken G, Kung SC, Raja R: Decrea sed erythropoietin requirements in maintenance hemodialysis patients with statin therapy. ASAIO J 2003;49:422-425.
91. Arabul M, Gullulu M, Yilmaz Y, Akdag I, Kahvecioglu S, Eren MA, Dilek K: Effect of fluvastatin on serum prohepcidin levels in patients with end-stage renal disease. Clin Biochem 2008; 41:1055-1058.
92. Suassuna PG, Bastos MG: Intermittent doses of statin in hemodialysis patients with spontaneous low LDL cholesterol levels. Arq Bras Cardiol 2008;90:104-111.
93. Bienvenu J, Doche C, Gutowski MC, Lenoble M, Lepape A, Perdrix JP: Production of proinflammatory cytokines and cytokines involved in the TH1/TH2 balance is modulated by pentoxif ylline. J Cardiovasc Pha rmacol 1995; 25:80-84.
94. Cooper A, Mikhail A, Lethbridge MW, Kemeny DM, Macdougall IC: Pentoxifylline improves hemoglobin levels in patients with erythropoietin- resistant anemia in renal failure. J Am Soc Nephrol 2004;15:1877-1882.
95. Johnson DW, Hawley CM, Rosser B, Beller E, Thompson C, Fassett RG, Ferrari P, Mac-Donald S, Pedagogos E, Cass A: BMC Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial. Nephrol 2008; 9:8.
96. Angelillo-Scherrer A, Burnier L, Lambrechts D, Fish RJ, Tjwa M, Plaisance S, Sugamele R, DeMol M, Martinez-Soria E, Maxwell PH, Lemke G, Goff SP, Matsushima GK, Earp HS, Chans on M, Collen D, Izui S, Schapira M, Conway EM, Carmeliet P: Role of Gas6 in erythropoiesis and anemia in mice. J Clin Invest 2008; 118:583-596.
97. Nakamoto H, Mimura T, Honda N: Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis. Hemodial Int 2008; (suppl 2):9-14.
98. Deicher R and Hörl WH: Hormonal adjuvants for the treatment of renal anaemia Eur J Clin Invest 2005; 35:75-84.