3000bp (erythropoietin, EPO) 1953,Erslev 27 C ( recombined human erythropoietin,

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1 Urology and nephrology FMS,Nov 2004,Vol. 24 NO. 6 Ξ ( EPO) (rhue2 PO), EPO rhuepo ; ; [ ]R692 [ ] A [ ] (2004) , EPO 1977 Miyake [1 ] [2 1906, ] 1985 Carnot, [2 ], EPO 3000bp (erythropoietin, EPO) 1953,Erslev EPO 193,N [2 ] EPO 27 C ( recombined human erythropoietin, rhuepo) 1989, FDA rhuepo, rhuepo EPO, ( end stage renal dis2 EPO d ease,esrd), EPO [2,3 40 % ] EPO [1 ] Asn24 Asn38 Asn83 N - rhuepo, N - 1 EPO 1. 1 EPO, 7, 5 4 EPO 165, 18240d [2 ], [2,3,5 ], EPO EPO 13 Essary LR, Wick MR. Cutaneous calciphylaxis, an underrecongnized calinicopathologic entity. Am J Clin Pathol,2000,113 (2) : Russell R,Brookshire MA,Zekonis M,et al. Distal calcific uremic arteri2 olopathy in a hemodialysis patient responds to lowering of Ca x P product and aggressive wound care. Clin Nephrol,2002,58 (3) : Malluche HW,Monier - Faugere MC. Hyperphosphatemia :pharmacologic intervention yesterday, today and tomorrow. Clin Nephrol,2000,54 (4) : Don BR,Chin AI. A strategy for the treatment of calcific uremic arteri2 olopathy(calciphylaxis) employing a combination of therapies,2003,59 (6) : Green JA, Green CR,Minott SD. Calciphylaxis treated with neurolytic lumbar sympathetic block : case repot and review of the literature. Reg Anesth Pain Med,2000,25 (3) : Cicone JS,Petronis JB, Embert CD,et al. Successful treatment of calci2 phylaxis with intravenous sodium thiosulfate. Am J Kidney Dis,2004,43 (6) : Hafner J, Keusch G, Wahl C,et al. Calciphylaxis : a syndrome of skin necrosis and acrol ganarene in chronic renal failure. Vasa,1998,27 (3) : Mazhar AR,Johnson RJ,Gillen D,et al. Risk factors and mortality asso2 ciated with calciphylaxis in end - stage renal disease. Kidney Int,2001, 60(1) : ( : ) Ξ :100034,

2 Urology and nephrology FMS,Nov 2004,Vol. 24 NO EPO 10 %,, EPO ] N - EPO, EPO, EPO ; EPO [1 ] N -, EPO EPO EPO EPO N -, EPO EPO EPO [4 ], EPO EPO EPO, Ser126 O -, EPO EPO EPO ] EPO , 33, EPO, [2,4 ] EPO EPO EPO, ] Nathan 1964 EPO EPO Denny ESRD ( EPO GCSF GMCSF GH PRL ),, EPO, EPO, EPO EPO EPO,4 ] 152,5 ], 80 % EPO - mrna 166 EPO, 131 [4,5 150 EPO, ], EPO D 150 EPO [1 ], 160 ] 1. 2 EPO, 20 % EPO - mrna 20 %, EPO - mrna 30 % 1957,Jacobson 40 %, EPO EPO, EPO, EPO ] [4 ],,EPO - mrna EPO - mrna [1,4 ] EPO - mrna 1. 3 EPO [5 ] EPO, EPO - mrna 5 -, [5 ] EPO [5 ], EPO,, Koury Goldberg EPO (hemoglobin,hb),, Hb, Hb EPO, EPO,EPO,, EPO EPO Hb, EPO, EPO Acker EPO - mrna b,,epo H 2 O 2, NAD

3 Urology and nephrology FMS,Nov 2004,Vol. 24 NO. 6 (P) H, O 2 2 EPO H 2 O 2 ; H 2 O 2, 2. 1 EPO [8 EPO mrna ],Fandrey, Hep G2 EPO mrna,h 2 O 2 EPO,, 1 100, , EPO [4 EPO, 6 24 ] Hep G2, EPO : EPO 1 EPO ; NO EPO [6 ] 2 c - myc RNA [7 NO EPO ] mrna ; EPO ;12 Hb ;12 14 EPO [2 ], Krantz EPO FVA (friend EPO virus that produce anemia), 6, CFU - E EPO EPO mrna,12, EPO CFU - E ; 48 60, (SCF,GM - CSF, IL - 3 IGF - 1) 24, [8, CFU - E ] EPO 2. 2 EPO, EPO EPO EPO,, 5 [9 EPO ], EPO,,EPO [11 ] (chronic re2 nal failure,crf) EPO EPO mrna EPO, EPO [12, ] EPO EPO ( ), stat5 EPO EPO [5, ],, EPO rhuepo Hct < 25 %, EPO,60 % (, < 20 % / < 100 ng/ ml), EPO EPO 2. 3 EPO,, NO EPO GFR < 20 ml/ min 30 ml/ min [10 ] : :

4 Urology and nephrology FMS,Nov 2004,Vol. 24 NO , ; : [17 ], EPO ARF ; ARF : EPO, EPO [13 ] EPO [18 ] ARF,, EPO,rHuEPO ARF EPO [13 EPO ] 3. 2 rhuepo EPO rhuepo CRF, : EPO rhuepo, 25 % (acute renal failure,arf), [14 EPO ] [1 ] rhuepo CRF,, rhuepo 3 rhuepo, rhuepo 3. 1 rhuepo EPO NO 20,rHuEPO - 1, EPO,, rhuepo K/ DOQI, rhue2 Besarab PO ESRD Hct Hct, Hct rhuepo 39 %, Hct 29 % rhuepo ESRD CRF, rhuepo, rhuepo, [1 ], EPO [15 ] Mih ly, rhuepo rhuepo ESRD CRF, EPO HIV 3. 3 rhuepo 4 6, EPO (rhuepo 450 kg kg - 1-1,96 % Hb/ Hct [2 ) ] EPO, rhuepo CRF EPO :, ARF :CRF < 100 rhuepo, ng/ ml / < 20 % 1990,,, ARF rhuepo rhuepo ARF 15 % [16 ] [1, EPO, ] ARF 2001, rhuepo ARF, EPO

5 Urology and nephrology FMS,Nov 2004,Vol. 24 NO. 6,, PRCA ; :,,, rhuepo Drueke,, rhuepo 3. 4 [19 ] ; : ( novel erythro2 poiesis stimulating protein,nesp) NESP ( IL - 1, EPO 5 2 TNF - ) rhuepo CRP N, rhuepo 3 rhuepo ; (25. 3 hrs vs 8. 5 hrs) rhuepo 2 ACEI : (48. 8 hrs vs hrs), ACEI, Hb NESP Hct EPO EPO CRF, NESP rhuepo, : EPO mrna,, ACEI EPO [20 ] ; ACEI IL - 12 ] ; BFU - E AT - EPO,AT - BFU - E ACEI AT - ; ACEI EPO, ACEI EPO [21 ] L - : L -, L - ; : PTH PTH EPO rhuepo [1 rhuepo ] 1998 rhuepo ( EPO - ) (pure red cell aplasia, PRCA) PRCA, rhuepo PRCA EPO, rhuepo EPO, EPO PRCA [22 ] 1 Tong EM, Nissenson AR. Erythropoietin and anemia. Semin Nephrol, 2001,21 (2) : Fisher JW. Erythropoietin : Physiologic and Pharmacologic Aspects. Proc Soc Exp Biol Med,1997,216(3) : Koury ST, Koury MJ. Erythropoietin production by the kidney. Semin Nephrol, 1993,13 (1) : Eckardt KU. Erythropoietin :oxygen - dependent control of erythropoiesis and its failure inrenal disease. Nephron,1994,67 (1) : Sasaki R,Masuda S,Nagao M. Erythropoietin :multiple physiological func2 tions and regulation of biosynthesis. Biosci Biotechnol Biochem,2000,64 (9) : Yoshioka K, Fisher JW. Nitric oxide enhancement of erythropoietin pro2 duction in the isolated perfused rat kidney. Am J Physiol,1995,269 (4 Pt 1) :C Todorov V,Gess B, Godecke A,et al. Endogenous nitric oxide attenuates erythropoietin gene expression in vivo. Pflugers Arch,2000,439 (4) : Fisher JW. Erythropoietin :physiology and pharmacology update. Exp Biol Med(Maywood),2003,228(1) : Gabrilove J. Overview :erythropoiesis,anemia,and the impact of erythro2 poietin. Semin Hematol,2000,37 (4 Suppl 6) : Juul S. Erythropoietin in the central nervous system,and its use to pre2 vent hypoxic - ischemic brain damage. Acta Paediatr Suppl, 2002, 91 (438) : Adamson J. Erythropoietin,iron metabolism,and red blood cell produc2 tion. Semin Hematol,1996,33(2 Suppl 2) :5-7

6 Urology and nephrology FMS,Nov 2004,Vol. 24 NO Ξ, ; [ ]R692 [ ] A [ ] (2004) (statins) A, ( 32hydroxy232methylglutaryl coenzyme A [ HMG2CoA] reductase inhibitors),, 1, ( end2stage renal dis2 ease,esrd) ( Coronary Artery Disease,CAD), ( < 50 ml/ min) 12 Majdan M,Ksiazek A,Koziol M,et al. Comparison of plasma erythropoi2 etin concentrations and iron status in hemodialyzed patients not requiring and requiring rhuepo therapy. Nephron,1996,73 (3) : Eckardt KU. Pathophysiology of renal anemia. Clin Nephrol,2000,53 (1 Suppl 1) :S Lipkin GW, Kendall RG, Russon LJ,et al. Erythropoietin Deficiency in Acute Renal Failure. Nephrol Dial Transplant,1990,5(11) : Tucker B, Fabbian F, Giles M,et al. Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic renal failure. Nephrol Dial Transplant,1997,12 (4) : Nagano N,Koumegawa J,Arai H,et al. Effect of recombinant human ery2 thropoietin on new anaemic model rats induced by gentamicin. J Pharm Pharmacol,1990,42 (11) : Bagnis C,Beaufils H,Jacquiaud C,et al. Erythropoietin enhances recov2 ery after cisplatin - induced acute renal failure in the rat. Nephrol Dial Transplant,2001,16(5) : Nemoto T, Yokota N, Keane WF, et al. Recombinant erythropoietin rapidly treats anemia in ischemic acute renal failure. Kidney Int,2001, 59(1) : Casadevall N. Cellular mechanism of resistance to erythropoietin. Nephrol Dial Transplant,1995,10 Suppl 6 : Gossmann J,Thurmann P,Bachmann T,et al. Mechanism of angiotens in converting enzyme inhibitor - related anemia in renal transplant recipi2 ents. Kidney Int,1996,50(3) : Matsumura M,Nomura H,Koni I,et al. Angiotensin - converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Nephron, 1997,77 (2) : Locatelli F,Del Vecchio L. Pure red cell aplasia secondary to treatment with erythropoietin.j Nephrol,2003,16 (4) : ( : ) :330006,

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