Protein Information

Name erythropoietin
Synonyms EP; EPO; Epoetin; Erythropoietin; Erythropoietin precursor; Epoetins; Erythropoietins; Erythropoietin precursors

Compound Information

Name ferrous sulfate
CAS sulfuric acid iron(2+) salt (1:1)

Reference List

PubMed Abstract RScore(About this table)
9550669 Duranay M, Bali M, Sahin M, Yakinci G, Vurgun N, Dilmen U: Parvovirus B19 infection and unresponsiveness to erythropoietin therapy in haemodialysis patients. Nephrol Dial Transplant. 1998 Mar;13(3):779-80.

1(0,0,0,1) Details
9115299 Melillo G, Taylor LS, Brooks A, Musso T, Cox GW, Varesio L: Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine. J Biol Chem. 1997 May 2;272(18):12236-43.


The iron chelator desferrioxamine (DFX) induces the activity of the human erythropoietin enhancer in Hep3B cells.
1(0,0,0,1) Details
15212134 Williams M, Blocksom JM, Baciewicz FA Jr: Coronary artery bypass grafting in a dialysis-dependent Jehovah's Witness. Tex Heart Inst J. 2004;31(2):181-3; discussion 183.

Coronary artery bypass grafting can be performed safely in the Jehovah's Witness patient with dialysis-dependent chronic renal failure by performing the operation electively if possible, limiting blood loss through the application of off-pump bypass and autologous transfusion techniques during surgery, increasing hemoglobin during both the pre- and postoperative periods by using erythropoietin and ferrous sulfate, and maintaining oxygen delivery during the postoperative period by the use of inotropic agents.
31(0,1,1,1) Details
10850644 Skikne BS, Ahluwalia N, Fergusson B, Chonko A, Cook JD: Effects of erythropoietin therapy on iron absorption in chronic renal failure. J Lab Clin Med. 2000 Jun;135(6):452-8.

The absorption of 50 mg of iron as ferrous sulfate increased 2.4-fold from 3.8% to 9.4% (P < .05) when given without food and 4.2-fold from 1.4% to 5.9% (P < .05) when given with food after erythropoietin administration.
15(0,0,1,10) Details
7677965 Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW: Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N Engl J Med. 1993 Jan 14;328(2):73-80.

8(0,0,0,8) Details
17338998 Beck-da-Silva L, Rohde LE, Pereira-Barretto AC, de Albuquerque D, Bocchi E, Vilas-Boas F, Moura LZ, Montera MW, Rassi S, Clausell N: Rationale and design of the IRON-HF study: a randomized trial to assess the effects of iron supplementation in heart failure patients with anemia. J Card Fail. 2007 Feb;13(1):14-7.

Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron.
Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks, ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks, or placebo.
1(0,0,0,1) Details
2299254 Goodnough LT, Brittenham GM: Limitations of the erythropoietic response to serial phlebotomy: implications for autologous blood donor programs. J Lab Clin Med. 1990 Jan;115(1):28-35.

This report also indicates that a significant number of AB units have red cell volumes below minimum standards for blood donation, which has important implications in a risk/benefit analysis of whether nontransfused AB units should be "crossed-over" for HB transfusion, and that future studies designed to maximize AB procurement should include an evaluation of recombinant erythropoietin therapy in AB programs and therapeutic alternatives to ferrous sulfate as iron supplementation in AB donors.
7(0,0,1,2) Details
12481145 Trivedi HS, Brooks BJ: Erythropoietin therapy in pre-dialysis patients with chronic renal failure: lack of need for parenteral iron. Am J Nephrol. 2003 Mar-Apr;23(2):78-85.

7(0,0,0,7) Details
10778761 Smaniotto D, Luzi S, Morganti AG, Cellini N: Prognostic significance of anemia and role of erythropoietin in radiation therapy. Tumori. 2000 Jan-Feb;86(1):17-23.

The results of a series of clinical studies published in the last decade allow some general observations: 1. the administration of erythropoietin, especially if associated to ferrous sulfate is able to increase hemoglobulin levels in cancer patients undergoing radiation therapy (combined with concomitant chemotherapy); 2. erythropoietin stimulation of hemoglobin in anemia decreases the need for blood transfusion in cancer patients; 3. tumor response to radiation therapy appears to be enhanced by erythropoietin-induced hemoglobulin increase.
7(0,0,1,2) Details
1542922 Biesma DH, Kraaijenhagen RJ, Poortman J, Marx JJ, van de Wiel A: The effect of oral iron supplementation on erythropoiesis in autologous blood donors. Transfusion. 1992 Feb;32(2):162-5.

During the preoperative period, in which 4 units of blood were collected, 17 patients received oral iron supplementation with 287 mg of ferrous sulfate (105 mg of elemental iron/day), while 17 patients did not use any iron supplementation.
In both iron-supplemented and control patients, serum erythropoietin levels returned to initial values within a few days after surgery.
1(0,0,0,1) Details
8171147 Polley JW, Berkowitz RA, McDonald TB, Cohen M, Figueroa A, Penney DW: Craniomaxillofacial surgery in the Jehovah's Witness patient. Plast Reconstr Surg. 1994 May;93(6):1258-63.

A management protocol was developed utilizing preoperative erythropoietin and ferrous sulfate therapy, intraoperative in-line normovolemic hemodilution, and meticulous intraoperative hemostasis which allows us to perform major craniomaxillofacial reconstructions in Jehovah's Witness patients without the use of homologous or predonated autologous blood transfusions.
6(0,0,1,1) Details
8083076 Dusenbery KE, McGuire WA, Holt PJ, Carson LF, Fowler JM, Twiggs LB, Potish RA: Erythropoietin increases hemoglobin during radiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys. 1994 Jul 30;29(5):1079-84.

Fifteen were treated with r-HuEPO (200 U/kg/day) and ferrous sulfate 5-10 days prior to initiation of external beam radiation therapy, continuing until Hgb was < or = 14 g/dL or completion of radiation therapy.
4(0,0,0,4) Details
8459128 Masai T, Sakakibara T, Watanabe S, Akedo H, Furutani Y, Kodama K: [2 cases report of open heart surgery with non-blood transfusion in severe valvular heart disease with cardiac cachexia--the efficacy of recombinant human erythropoietin]. Nippon Kyobu Geka Gakkai Zasshi. 1993 Jan;41(1):105-10.

Both patients were administered 9000-18000 U/week of EPO and ferrous sulfate pre- and postoperatively.
1(0,0,0,1) Details
7872321 Wingard RL, Parker RA, Ismail N, Hakim RM: Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin. Am J Kidney Dis. 1995 Mar;25(3):433-9.

These four preparations included Chromagen (ferrous fumarate; Savage Laboratories, Melville, NY), Feosol (ferrous sulfate; SmithKline Beecham, Inc, Pittsburgh, PA), Niferex (polysaccharide; Central Pharmaceuticals, Inc, Seymour, IN), or Tabron (ferrous fumarate; Parke-Davis, Morris Plains, NJ).
4(0,0,0,4) Details
11252534 Markova M, Haluzik M, Svobodova J, Rosicka M, Nedvidkova J, Haas T: Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment. Physiol Res. 2000;49(6):679-84.


The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment.
4(0,0,0,4) Details
9756115 Bhandari S, Brownjohn A, Turney J: Effective utilization of erythropoietin with intravenous iron therapy. J Clin Pharm Ther. 1998 Feb;23(1):73-8.

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8967587 Soukup J, Menzel M, Roth S, Radke J: [The perioperative use of recombinant erythropoietin (rhEPO) in Jehovah's witnesses]. Anaesthesist. 1996 Aug;45(8):745-9.

After preoperative subcutaneous application of 5000 I.E. rhEPO three times per week and daily oral substitution of 300 mg ferrous sulfate over a period of 3 weeks, the Hb increased to 15.5 g/dl and the HCt to 49%.
3(0,0,0,3) Details
12118656 Kalu E, Wayne C, Croucher C, Findley I, Manyonda I: Triplet pregnancy in a Jehovah's witness: recombinant human erythropoietin and iron supplementation for minimising the risks of excessive blood loss. BJOG. 2002 Jun;109(6):723-5.

1(0,0,0,1) Details
14655280 Markova M, Haluzik M, Jiskra J, Haluzikova D, Svobodova J, Rosicka M: [Effect of sideropenic anemia and its therapy on serum levels of leptin] . Cas Lek Cesk. 2001 Dec 6;140(24):767-9.


Blood count, serum leptin, erythropoietin (EPO) and transpherine receptor (TfR) levels were estimated in all samples.
1(0,0,0,1) Details
17448971 Cuenca J, Garcia-Erce JA, Martinez F, Cardona R, Perez-Serrano L, Munoz M: Preoperative haematinics and transfusion protocol reduce the need for transfusion after total knee replacement. Int J Surg. 2007 Apr;5(2):89-94. Epub 2006 Apr 27.


CONCLUSION: This protocol seems to be effective for avoiding ABT in non-anaemic TKR patients, whereas for anaemic patients another blood saving strategy, such us preoperative erythropoietin administration or postoperative blood salvage, should be added to further increase its effectiveness.
1(0,0,0,1) Details
11465435 Christopoulou M, Derartinian H, Hatzidimitriou G, Iatrou L: Autologous blood transfusion in oral and maxillofacial surgery patients with the use of erythropoietin. J Craniomaxillofac Surg. 2001 Apr;29(2):118-25.

3(0,0,0,3) Details
7771487 Shrivastava D, Rao TK, Sinert R, Khurana E, Lundin AP, Friedman EA: The efficacy of erythropoietin in human immunodeficiency virus-infected end-stage renal disease patients treated by maintenance hemodialysis. Am J Kidney Dis. 1995 Jun;25(6):904-9.

3(0,0,0,3) Details
9297428 Javier Manchon G, Natal Pujol A, Coroleu Lletget W, Zuasnabar Cotro A, Badia Barnusell J, Junca Piera J, Bel Comos J, Sabado Alvarez C, Prats Vinas J: [Randomized multi-center trial of the administration of erythropoietin in anemia of prematurity]. An Esp Pediatr. 1997 Jun;46(6):587-92.

Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day.
3(0,0,0,3) Details
1431504 Skikne BS, Cook JD: Effect of enhanced erythropoiesis on iron absorption. J Lab Clin Med. 1992 Nov;120(5):746-51.

To examine the influence of erythropoiesis on iron absorption, radioiron absorption tests were performed in normal subjects before and after a course of recombinant erythropoietin.
The absorption of heme and nonheme iron from a standard meal was measured in nine subjects, and the absorption of a therapeutic dose of ferrous sulfate given with or without food was determined in an additional 11 subjects.
3(0,0,0,3) Details
11887827 Johnson DW, Herzig KA, Gissane R, Campbell SB, Hawley CM, Isbel NM: Oral versus intravenous iron supplementation in peritoneal dialysis patients. Perit Dial Int. 2001;21 Suppl 3:S231-5.


The vast majority of erythropoietin (EPO)-treated peritoneal dialysis (PD) patients require iron supplementation.
1(0,0,0,1) Details
10343955 Antunes I, Resende C, Granjo E, Mesquita-Guimares J: Recombinant human erythropoietin alpha in the correction of anaemia in epidermolysis bullosa. J Eur Acad Dermatol Venereol. 1999 Mar;12(2):181-2.

1(0,0,0,1) Details
2757026 Van Wyck DB: Iron management during recombinant human erythropoietin therapy. Am J Kidney Dis. 1989 Aug;14(2 Suppl 1):9-13.

In all patients except those with transfusional iron overload, prophylactic supplementation with ferrous sulfate (325 mg up to three times daily) is recommended.
2(0,0,0,2) Details
8659499 Silverberg DS, Iaina A, Peer G, Kaplan E, Levi BA, Frank N, Steinbruch S, Blum M: Intravenous iron supplementation for the treatment of the anemia of moderate to severe chronic renal failure patients not receiving dialysis. Am J Kidney Dis. 1996 Feb;27(2):234-8.


Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given.
2(0,0,0,2) Details
8600865 Green D, Lawler M, Rosen M, Bloom S, Duerden M, Turba R, Kern H, Kirschner K, Ronin D: Recombinant human erythropoietin: effect on the functional performance of anemic orthopedic patients. Arch Phys Med Rehabil. 1996 Mar;77(3):242-6.

All patients received ferrous sulfate.
2(0,0,0,2) Details
8428002 Brugnara C, Chambers LA, Malynn E, Goldberg MA, Kruskall MS: Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects. Blood. 1993 Feb 15;81(4):956-64.

All healthy subjects took oral ferrous sulfate.
2(0,0,0,2) Details
12640375 Juul SE, Zerzan JC, Strandjord TP, Woodrum DE: Zinc protoporphyrin/heme as an indicator of iron status in NICU patients. J Pediatr. 2003 Mar;142(3):273-8.


Gestational age, growth variables, iron supplementation, erythropoietin treatment, and blood transfusions were documented.
2(0,0,0,2) Details
7934135 Stone RM, Bernstein SH, Demetri G, Facklam DP, Arthur K, Andersen J, Aster JC, Kufe D: Therapy with recombinant human erythropoietin in patients with myelodysplastic syndromes. Leuk Res. 1994 Oct;18(10):769-76.

Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients).
2(0,0,0,2) Details
19469261 Nikitin EN, Krasnoperova OV, Nikitin IuE: [Experience in the treatment of iron deficiency anemia with ferro-folgamma]. Klin Med. 2009;87(3):64-7.


Criteria for the efficiency were changes in clinical symptoms of anemia, hemoglobin level, erythrocyte and reticulocyte counts, packed cell volume, erythrocyte indices (mean erythrocyte volume, average content and concentration of hemoglobin in erythrocytes), erythropoietin level, and characteristics of iron metabolism (serum iron and ferritin levels, total iron-binding capacity of the serum, coefficient of ferritin saturation with iron), and drug tolerance.
2(0,0,0,2) Details
8417806 Nagel RL, Vichinsky E, Shah M, Johnson R, Spadacino E, Fabry ME, Mangahas L, Abel R, Stamatoyannopoulos G: F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study. Blood. 1993 Jan 1;81(1):9-14.

2(0,0,0,2) Details
7531047 Kubanek B, Rich I, Noe G: [Erythropoietin] . Infusionsther Transfusionsmed. 1994 Nov;21 Suppl 3:46-50.

A high dose of oral ferrous sulfate (300 mg) was given 11 days in advance of rHu EPO.
2(0,0,0,2) Details
11328902 Stoves J, Inglis H, Newstead CG: A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant. 2001 May;16(5):967-74.

2(0,0,0,2) Details
8411806 Inatsuchi H, Tanaka M, Masuda A, Arihara K, Katsuoka Y: [Preoperative collection of autologous blood with recombinant human erythropoietin therapy]. Nippon Hinyokika Gakkai Zasshi. 1993 Aug;84(8):1450-5.

All the patients were given ferrous sulfate 100 mg of iron orally every day.
2(0,0,0,2) Details
8262840 Lavey RS, Dempsey WH: Erythropoietin increases hemoglobin in cancer patients during radiation therapy. Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1147-52.

All 40 patients were given oral ferrous sulfate throughout their radiation therapy course.
2(0,0,0,2) Details
7529455 Bourantas KL, Georgiou I, Seferiadis K: Fetal globin stimulation during a short-term trial of erythropoietin in HbS/beta-thalassemia patients. Acta Haematol. 1994;92(2):79-82.

2(0,0,0,2) Details
2709674 Van Wyck DB, Stivelman JC, Ruiz J, Kirlin LF, Katz MA, Ogden DA: Iron status in patients receiving erythropoietin for dialysis-associated anemia. Kidney Int. 1989 Feb;35(2):712-6.

During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate.
2(0,0,0,2) Details
7608597 Shinonaga M: [Changes in hematological indices, iron levels and marrow erythroids through autologous blood donation before cardiac surgery--predonation with versus without recombinant human erythropoietin]. Nippon Kyobu Geka Gakkai Zasshi. 1995 Apr;43(4):479-87.

A unit of autologous blood (200 ml) was to be donated every 3 or 4 days for 2 weeks. 200mg of ferrous sulfate was given orally every day in 10 patients (the simple donation group), while 200 U/kg of rEPO was given intravenously 3 times a week in combination with oral ferrous sulfate supplementation in 15 patients (the rEPO-treatment group).
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11083968 de la Torre Aguilar M, Gascon Jimenez FJ, Zapatero Martinez M, Guzman Cabanas J, Huertas Munoz D, Ruiz Gonzalez D, Jaraba Caballero P: [Prophylaxis of anemia of prematurity with erythropoietin. An Esp Pediatr. 2000 Sep;53(3):243-8.

A ferrous sulfate supplement was also administered orally (4-6 mg/kg/day) with a multivitamin complex.
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1680462 Bender FH, Piraino B: Polycythemia in diabetic patients on CAPD. Adv Perit Dial. 1991;7:77-80.

Prior to the development of polycythemia, ferritin levels were low and ferrous sulfate therapy was begun at a time the Hct values were 36 to 40%.
Erythropoietin levels were obtained in 2 patients, and were 22 U/L (Hct 51%) and less than 5 U/L (Hct 55%).
1(0,0,0,1) Details
18098311 Skoner JM, Wax MK: Microvascular free-tissue transfer for head and neck reconstruction in Jehovah's Witness patients. Head Neck. 2008 Apr;30(4):455-60.


Iron supplements and/or erythropoietin were administered perioperatively in 6 of the 7 microvascular reconstructions.
1(0,0,0,1) Details
16917084 Bailey DM, Robach P, Thomsen JJ, Lundby C: Erythropoietin depletes iron stores: antioxidant neuroprotection for ischemic stroke? Stroke. 2006 Oct;37(10):2453. Epub 2006 Aug 17.

1(0,0,0,1) Details
11045266 Ahsan N: Infusion of total dose iron versus oral iron supplementation in ambulatory peritoneal dialysis patients: a prospective, cross-over trial. Adv Perit Dial. 2000;16:80-4.

The study design included an oral phase [4 months, ferrous sulfate 325 mg (195 mg elemental iron), three times daily], a "wash-out" phase (1 month, no iron supplementation), and an ITDI phase [4 months, single infusion over 4 hours of 1 g iron dextran mixed in 1/2 normal saline].
Laboratory parameters were monitored monthly, and subcutaneous recombinant human erythropoietin (rHuEPO) doses were adjusted monthly to maintain a hematocrit above 33%.
1(0,0,0,1) Details
7634987 Demirturk L, Hulagu S, Yaylaci M, Altin M, Ozel M: Serum erythropoietin levels in patients with severe anemia secondary to inflammatory bowel disease and the use of recombinant human erythropoietin in patients with anemia refractory to treatment. Dis Colon Rectum. 1995 Aug;38(8):896-7.

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9247787 Kotaki M, Uday K, Henriquez M, Blum S, Dave M: Maintenance therapy with intravenous iron in hemodialysis patients receiving erythropoietin. Clin Nephrol. 1997 Jul;48(1):63-4.

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14769316 Kourtzis N, Pafilas D, Kasimatis G: Blood saving protocol in elective total knee arthroplasty. Am J Surg. 2004 Feb;187(2):261-7.


It is based on perioperative administration of human recombinant erythropoietin plus iron and folic acid, mild acute normovolemic hemodilution, meticulous surgical technique, postoperative blood salvage through a closed-wound drainage system, and lower transfusion triggers.
1(0,0,0,1) Details
9328369 Ahluwalia N, Skikne BS, Savin V, Chonko A: Markers of masked iron deficiency and effectiveness of EPO therapy in chronic renal failure. Am J Kidney Dis. 1997 Oct;30(4):532-41.


Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease.
1(0,0,0,1) Details
11214425 Podesta A, Carmagnini E, Parodi E, Dottori V, Crivellari R, Barberis L, Audo A, Lijoi A, Passerone G: Elective coronary and valve surgery without blood transfusion in patients treated with recombinant human erythropoietin (epoetin-alpha). Minerva Cardioangiol. 2000 Nov;48(11):341-7.

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8723587 Gombotz H: Subcutaneous epoetin alfa as an adjunct to autologous blood donation before elective coronary artery bypass graft surgery. Semin Hematol. 1996 Apr;33(2 Suppl 2):69-70; discussion 71-2.


Recombinant human erythropoietin (rHuEPO) has been used to facilitate AB donation and minimize the accompanying decrease in Hb levels in patients scheduled for cardiac surgery.
1(0,0,0,1) Details
11990314 Athanasiou-Metaxa M, Economou M, Tsantali C, Koussi A, Gombakis N: Congenital erythrocytosis with increased erythropoietin level. J Pediatr Hematol Oncol. 2002 Mar-Apr;24(3):234-6.

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10873876 Goicoechea M, Caramelo C, Ochando A, Andrea C, Garvia R, Ortiz A: Antiplatelet therapy alters iron requirements in hemodialysis patients. Am J Kidney Dis. 2000 Jul;36(1):80-7.


Hemodialysis (HD) patients are prone to develop iron deficiency because of consumption of iron stores during erythropoietin (EPO) therapy.
1(0,0,0,1) Details
10516989 Yamaguchi T, Baxter JG, Maebashi N, Asano T: Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. Ren Fail. 1999 Sep;21(5):453-68.

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia.
High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone.
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1361760 Domoto DT, Martin KJ: Failure of CAPD patients to respond to an oral iron absorption test. Adv Perit Dial. 1992;8:102-4.

CAPD patients require supplemental iron to maintain a response to erythropoietin.
Serum irons were measured at baseline in a fasting state and repeated two hours after the ingestion of 325 mgs ferrous sulfate in five CAPD patients.
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16253714 Goshorn J, Youell TD: Darbepoetin alfa treatment for post-renal transplantation anemia during pregnancy. Am J Kidney Dis. 2005 Nov;46(5):e81-6.


Darbepoetin alfa (Aranesp; Amgen Inc, Thousand Oaks, CA) is a unique erythropoiesis-stimulating protein that can be administered at an extended dosing interval relative to recombinant human erythropoietin because of its approximately 3-fold longer serum half-life.
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18986010 Factor KF: Anemia management in peritoneal dialysis patients: can an iron supplement maintain a normal transferrin saturation and hemoglobin level?. Adv Perit Dial. 2008;24:96-8.


The primary cause of anemia in dialysis patients is inadequate production of erythropoietin (EPO) by the dysfunctional kidneys.
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