*,*******,** * ** *** 1983 1985 National Kidney Foundation s Kidney Disease Outcome Quality Initiative Guidelines (NKF K/DOQI Guidelines) 11 12 g/dl [1] [2] [2] / C B12 B6E (L-carnitine) ferritin100 μg/l ferritin100 μg/l transferrin saturation20% [1,2] NKF K/DOQI Guidelines ferritin 200 μg/ltransferrin saturation 20%[3] ferritin transferrin saturation 100 μ g/l 20%[3] ferritin 500 μg/lferritin 500 μg/l transferrin saturation [3] [3] 6 101000 mg 1 2 25 100 mg [2] 3 96 19 3 145
ferritin transferrin saturation [1] iron sucrose iron dextran iron gluconate iron dextran 40 [4] (ferritin800 μ g/l transferrin saturation50%) C C C 50 200 mg [5,6] C ferritin transferrin Tarng C 300 mg 8 [7] ferritinzinc protoporphyrin (e-zpp) transferrin saturation ferritin e-zpp transferrin saturation Tarng e-zpp105 μmol/mol heme transferrin saturation25% C [8] NKF K/DOQI Guidelines C [3] ferritin500 μ g/l transferrin saturation30% C C [8] C [9] C D [10] [11] D Goicoechea calcijex1228 19 i-pth10.6 1.5 g/dl 12.2 1.5 g/dl i-pth [12] Abitar alfacalcidol 3 8.7 1.2 g/dl 10.3 0.8 g/dl [13] D i-pth [12,13,14] D D (megaloblastic anemia) 146 96 19 3
[15] Pronai (mean cell volume) 10mg [16]Sunder-Plassmann homocysteine[17] 2 3 mg [5,6] B 12 B 12 3 5B 12 B 12 250 μg [5,6] homocysteine Kuo 28 B 12 500 μ g 2homocysteine 23.9 5.02 μ mol/l 19.7 6.7 μ mol/l 25% 15 μ mol/l[18] Chen 45 B 12 1000 μg 2homocysteine 23.33 9.27 μmol/l 19.69 6.67 μ mol/l [19]B 12 homocysteineb 12 1000 μg B 6 B 6 (heme) B 6 B 6 B 6 [20] B 6 NKF K/DOQI Guidelines B 6 [3] B 6 100 150 mg [5,6] E E (oxidative stress) E E Miyazaki E (oxidized low density lipoprotein) [21] Tarng E DNA [22]E Cristol E 500 mg 20 30% [23]Németh E 15 mg/kg [24] E Roob 6E 1200 IU 96 19 3 147
(all-rac-α -tocopheryl acetate)iron sucrose [25] (carnitine) (lysine) (methionine) (levo) (dextro) β - ( carnitine palmitoyltransferase I ) carnitine palmitoyltransferase II β - β - A (acyl-coa) (free carnitine)(acyl carnitine) (acyl carnitine: free carnitine)0.4 [6] [6]ATP pentosephosphate shunt [26] Golper [27] Labonia 6 38% [28] NKF K/DOQI Guidelines [3]NKF Carnitine Consensus Conference (dialysisrelated carnitine disorder) [29] NKF Carnitine Consensus Conference 20 mg/kg3 9 12 [29] [30]1999 FDA 15% trimethylamine (TMA) trimethylamine-noxide (TMAO) TMA dimethylamine [30] 0.5 g 2 g [31,32] 148 96 19 3
Ballal Gaughan [33,34]Berns [35] Teruel 5018 200 mg nadrolone decanoate 6 5022 ( 6000 u) [36] nadrolone decanoate NKF K/DOQI Guidelines [3] OPTA(optimal treatment of renal anemia initiative) 50 PSA (prostate specific antigen) [2] (GH IGF-1 IL-3 pentoxiphylline) GH (growth hormone) [37,38] IGF-1 (insulin-like growth factor-1) IL-3 (interleukin-3)(in vitro study)[37,39,40] IGF-1 IGF-1 GH IGF-1 IGF-1 [37] Cooperpentoxipylline TNF-α (tumor necrosis factor-α) IFN-γ (interferon-γ) proinflammatory cytokines [41] 11 12 g/dl / (bone marrow 96 19 3 149
fibrosis) D i-pth i-pth D C ferritin e-zpp 105 μmol/mol heme transferrin saturation 25% C ferritin500 μg/l transferrin saturation30% C B 12 B 6 B 12 B 6 B 12 homocysteine E GH IGF-1 IL-3 pentoxiphylline 1. Eschbach J, DeOreo P, Adamson J, et al: NKF-K/DOQI Clinical practice guidelines for anemia of chronic renal disease: update 2000. Am J Kidney Dis 2001; 37(suppl 1): S182-238. 2. Hörl WH, Vanrenterghem Y: Optimal treatment of renal anemia (OPTA): improving the efficacy and efficiency of renal anemia therapy in haemodialysis patients receiving intravenous epoetin. Nephrol Dial Transplant 2005; 20(suppl 3): iii25-32. 3. Adamson JW, Bailie GR, Berns JS, et al: Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease in Adults. Am J Kidney Dis 2006; 47(suppl 3): S16-108. 4. Hörl WH: Adjunctive therapy in anemia management. Nephrol Dial Transplant 2002; 17(suppl 5): 56-9. 5. Descombes E, Hanck AB, Fellay G: Water soluble vitamins in chronic hemodialysis patients and need for supplementation. Kidney Int 1993; 43: 1319-28. 6. Hörl WH: Is there a role for adjuvant therapy in patients being treated with epoetin? Nephrol Dial Transplant 1999; 14(suppl 2): 50-60. 7. Tarng DC, Huang TP, Chen TW, Yang WC: Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. Kidney Int 1999; 55(suppl 69): S107-S118. 8. Tarng DC, Wei YH, Huang TP, Kuo BIT, Yang WC: Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int 1999; 55: 2477-86. 9. Rolton HA, McConnel KM, Modi KS, Macdougall AI: The effect of vitamin C intake on plasma oxalate in patients on regular hemodialysis. Nephrol Dial Transplant 1991; 6: 440-3. 10. Rao DS, Shih MS, Mohini R: Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med 1993; 328: 171-5. 11. Barbour GL: Effect of parathyroidectomy on anemia in chronic renal failure. Arch Intern Med 1979; 139: 889-91. 12. Goicoechea M, Vazquez MI, Ruiz MA, Gomez-Campdera F, Perez-García R, Valderrábano F: Intravenous calcitriol improves anemia and reduces the need for erythropoietin in hemodialysis patients. Nephron 1998; 78: 23-7. 13. Albitar S, Genin R, Fen-Chong M, Serveaus M-O, Schohn D, Chuet C: High-dose alfacalcidol improves anaemia in patients on haemodialysis. Nephrol Dial Transplant 1997; 12: 514-8. 14. Argilés A, Mourad G, Lorho R, et al: Medical treatment of severe hyperparathyroidism and its influence on anaemia in end-stage renal failure. Nephrol Dial Transplant 1994; 9: 1809-12. 15. Ono K, Hisasue Y: Is folate supplementation necessary in hemodialysis patients on erythropoietin therapy? Clin Nephrol 1992; 38: 290-2. 16. Pronai W, Riegler-Keil M, Silberbauer K, Stockenhuber F: Folic acid supplementation improves erythropoietin therapy? Clin Nephrol 1992; 38: 290-2. 17. Sunder-Plassmann G, Födinger M, Buchmayer H, et al: Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study. J Am Soc Nephrol 2000; 11: 1106-16. 18. Kuo HT, Tsai JC, Chen LN, et al: Independent effect of methylcobalamin on hyperhomocysteinemia in hemodialysis 150 96 19 3
patients. Acta Nephrol 2000; 14: 261. 19. B12 2002 14 163-6 20. Mydlik M, Derzsiova K, Zemberova E: Metabolism of vitamin B6 and its requirement in chronic renal failure. Kidney Int 1997; 52(suppl 62): S56-9. 21. Miyazaki H, Matsuoka H, Itabe H et al: Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin E-coated dialyzer. Circulation 2000; 101: 1002-6. 22. Tarng DC, Huang TP, Liu TY, Chen HW, Sung YJ, Wei YH: Effect of vitamin E-bonded membrane on the 8-hydrowy 2 -deoxyguanosine level in leukocyte DNA of hemodialysis patients. Kidney Int 2000; 58: 790-9. 23. Cristol JP, Bosc JY, Badiou S, et al: Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transplant 1997; 12: 2312-7. 24. Németh I, Turi S, Haszon I, Bereczki C: Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis. Pediatr Nephrol 2000; 14: 13-7. 25. Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM: Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 2000; 11: 539-49. 26. Boran M, Dalva I, Gönenç F, Çetin S: Response to recombinant human erythropoietin (r-hu EPO) and L-carnitine combination in patients with anemia of end-stage renal disease. Nephron 1996; 73: 314-5. 27. Golper TA, Ahmad S: L-carnitine administration to hemodialysis patients: has its time come? Semin Dial 1992; 5: 94-8. 28. Labonia WD: L-carnitine effects on anemia in hemodialyzed patients treated with erythropoietin. Am J Kidney Dis 1995; 26: 757-64. 29. Eknoyan G, Latos DL, Lindberg J: Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. Am J Kidney Dis 2003; 41: 868-76. 30. Evans A: Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis 2003; 41: S13-26. 31. Matsumoto Y, Amano I, Hirose S at al: Effects of L-carnitine supplementation on renal anemia in poor responders to erythropoietin. Blood Purif 2001; 19: 24-32. 32. Hsieh RY, Hsiao SJ, Cheng MF, Tseng CC, Huang JJ: Clinical efficacy of oral low-dose L-carnitine supplementation in chronic peritoneal dialysis patients: a preliminary report. Acta Nephrol 2004; 18: 8-15. 33. Ballal SH, Domoto DT, Polack DC, Marciulonis P, Martin KJ: Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease. Am J Kidney Dis 1991; 17: 29-33. 34. Gaughan WJ, Liss KA, Dunn SR, et al: A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients. Am J Kidney Dis 1997; 30: 495-500. 35. Bern JS, Rudnick MR, Cohen RM: A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis. Clin Nephrol 1992; 37: 264-7. 36. Teruel JL, Marcen R, Navarro-Antolin J, Aguilera A, Fernandez- Juarez G, Ortuňo J: Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study. J Am Soc Nephrol 1996; 7: 140-4. 37. Deicher R, Hörl WH: Hormonal adjuvants for the treatment of renal anemia. Eur J Clin Invest 2005; 35: 75-84. 38. Viidas U, Johannsson G, Mattson-Hulten L, Ahlmen J: Lipids, blood pressure and bone metabolism after growth hormone therapy in elderly hemodialysis patients. J Nephrol 2003; 16: 231-7. 39. Brox AG, Zhang F, Guyda H, Gagnon RF: Subtherapeutic erythropoietin and insulin-like growth factor-1 correct the anemia of chronic renal failure in mouse. Kidney Int 1996; 50: 937-43. 40. Shimizu T, Kawano Y, Takaue Y, Kuroda Y: Diminished erythropoietin-induced erythroid growth in patients with renal anemia is restored by recombinant human erythroid differentiation factor. Am J Hematol 1994; 47: 178-82. 41. 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: 1877-82. 96 19 3 151