Abstract
Anemia is a frequent complication of patients with chronic kidney disease (CKD). Anemia is defined as a hemoglobin level <11.5 g/dl in women and <13.5 g/dl in adult men (in elderly men <12.5 g/dl). Many factors contribute to renal anemia, such as erythropoietin deficiency, iron deficiency and/or medication. The development of anemia is often complicated by the co-morbidity of the patients, such as diabetes, hypertension, severe heart failure, neoplasia or inflammation.
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References
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.
Danielson B. R-HuEPO hyporesponsiveness: who and why? Nephrol Dial Transplant. 1995;10(Suppl. 2):69–73.
Hörl WH, Jacobs C, Macdougall IC et al. European Survey on Anaemia Management (ESAM). Nephrol Dial Transplant. 2000;15(Suppl. 4):43–5.
Allen DA, Breen C, Yaqoob MM, Macdougall IC. Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-y and TNF-α. J Invest Med. 1999;47:204–11.
Stenvinkel P, Alvestrand A. Inflammation in end-stage renal disease: sources, consequences, and therapy. Semin Dial. 2002;15:329–37.
Eschbach JW, Adamson JW. Anemia of end-stage renal disease (ESRD). Kidney Int. 1985;28:1–5.
Thomas MC, MacIsaac RJ, Tsalamandris C, Power D, Jerums G. Unrecognized anemia in patients with diabetes: a cross-sectional survey. Diabetes Care. 2003;26:1164–9.
Kazmi WH, Kausz AT, Khan S et al. Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis. 2001;38:803–12.
Hsu CY, McCulloch CE, Curban GC. Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination survey. J Am Soc Nephrol. 2002;13:504–10.
Kausz AT, Khan SS, Abichandani R et al. Management of patients with chronic renal insuffiency in the Northeastern United States. J Am Soc Nephrol. 2001;12:1501–7.
Valderrábano F, Hörl WH, Macdougall IC, Rossert J, Rutkowski B, Wauters JP. Pre-dialysis survey on anaemia management. Nephrol Dial Transplant. 2003;18:89–100.
Hörl WH, Macdougall IC, Rossert J, Rutkowski B, Wauters JP, Valderrábano F. Predialysis survey on anemia management: patient referral. Am J Kidney Dis. 2003;41: 49–61.
McClellan WM, Jurkovitz C, Abramson J. The epidemiology and control of anemia among pre-ESRD patients with chronic kidney disease. Eur J Clin Invest. 2004 (In press).
McClellan WM, Flanders WD, Langston RD, Jurkovitz C, Presley R. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol. 2002;13:1928–36.
Horwich TB, Fonarow GC, Hamilton MA, McClellan WR, Borenstein J. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol. 2002;39:1780–6.
Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with newonset heart failure. Circulation. 2003;107:223–5.
Langston RD, Presley R, Flanders WD, McClellan WM. Renal insufficiency and anemia are independent risk factors for death among patients with acute myocardial infarction admitted to community hospitals: a population-based study. Kidney Int. 2003;64:1398–405.
Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W. Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int. 2003;64:610–15.
Levin A, Thompson CR, Ethier L et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis. 1999;34:125–34.
London GM, Pannier B, Guerin AP et al. Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol. 2001;12:2759–67.
London GM, Pannier B, Guerin AP, Marchais SJ, Safar ME, Cuche JL. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: comparative effects of ACE inhibition and calcium channel blockade. Circulation. 1994;90:2786–96.
Ifudu O, Feldman J, Friedman EA. The intensity of hemodialysis and the response to erythropoietin in patients with end-stage renal disease. N Engl J Med. 1996;334: 420–5.
Silberberg J, Racine N, Barre P, Sniderman AD. Regression of left ventricular hypertrophy in dialysis patients following correction of anemia with recombinant human erythropoietin. Can J Cardiol. 1990;6:1–4.
Cannella G, La Canna G, Sandrini M et al. Reversal of left ventricular hypertrophy following recombinant human erythropoietin treatment of anaemic dialysed uremic patients. Nephrol Dial Transplant. 1991;6:31–7.
Möcks J, Franke W, Ehmer B et al. Analysis of safety database for long term epoetin beta treatment. A meta analysis covering 3697 patients. In: Koch KM, Stein G, editors. Pathogenetic and Therapeutic Aspects of Chronic Renal Failure. New York: Marcel Dekker, 1997:163–79.
Locatelli F, Conte F, Marcelli D. The impact of haematocrit levels and erythropoietin treatment on overall and cardiovascular mortality and morbidity — the experience of the Lombardy dialysis registry. Nephrol Dial Transplant. 1998;13:1642–4.
Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol. 1999;10:610–19.
Collins AJ. Influence of target hemoglobin in dialysis patients on morbidity and mortality. Kidney Int. 2002; 80(Suppl.):44–8.
Locatelli F, Pisoni RL, Combe C et al. Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2004;19:121–32
Canadian Erythropoietin Study Group. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Br J Pharmacol. 1990:300:573–8.
Keown PA. Quality of life in end-stage renal disease patients during recombinant erythropoietin therapy. The Canadian erythropoietin study. Contrib Nephrol. 1991; 88:81–6
Clyne N, Jogestrand T. Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients. Nephron. 1992;60:390–6
Valderrábano F. Quality of life benefits of early anaemia treatment. Nephrol Dial Transplant. 2000;15:23–8
Foley RN, Parfrey PS, Morgan J et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int. 2000;58:1325–35
McMahon LP, Mason K, Skinner SL et al. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant. 2000;15:1425–30
Cannella G, La Canna G, Sandrini M et al. Renormalization of high cardiac output and of left ventricular size following long-term recombinant human erythropoietin treatment of anemic dialyzed uremic patients. Clin Nephrol. 1990; 34:272–8
Macdougall IC, Lewis NP, Saunders MJ et al. Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. Lancet. 1990;335:489–93
Löw-Friedrich I, Grützmacher P, Marz W et al. Long-term echocardiographic examinations in chronic hemodialysis patients substituted with recombinant human erythropoietin. Blood Purif. 1990;8:272–8
Silberberg J, Racine N, Barre P et al. Regression of left ventricular hypertrophy in dialysis patients following correction of anemia with recombinant human erythropoietin. Can J Cardiol. 1990;6:1–4
Pascual J, Teruel JL, Moya JL et al. Regression of left ventricular hypertrophy after partial correction of anemia with erythropoietin in patients on hemodialysis: a prospective study. Clin Nephrol. 1991;35:280–7
Fellner SK, Lang RM, Neumann A et al. Cardiovascular consequences of correction of the anemia of renal failure with erythropoietin. Kidney Int. 1993;44:1309–15
Wizemann V, Schäfer R, Kramer W. Follow-up of cardiac changes induced by anemia compensation in normotensive hemodialysis patients with left-ventricular hypertrophy. Nephron. 1993;64:202–6
Foley RN, Parfrey PS, Harnett JD et al. The impact of anemia on cardiomyopathy, morbidity, and mortality in endstage renal disease. Am J Kidney Dis. 1996;28:53–61
Lim PS, Yeh CH, Hung TS. Effects of recombinant erythropoietin on echocardiographic findings in elderly dialysis patients. Nephrology. 1997;3:149–54
Hayashi T, Suzuki A, Shoji T et al. Cardiovascular effects of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis. 2000;35:250–6
Portoles J, Torralbo M, Martin P et al. Regression of left ventricular hypertrophy after partial correction of anemia with erythropoietin in patients on hemodialysis: a prospective study. Clin Nephrol. 1991;35:280–7
London GM, Pannier B, Guerin AP et al. Alterations of left ventricular hypertrophy in, and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol. 2001;12:2759–67
McMahon LP. Advances in anaemia management: current evidence. Nephrology. 2002;7:257–61
Furuland H, Linde T, Ahlmén J et al. A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant. 2003;28:353–61
Besarab A, Bolton WK, Browne JK et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584–90
Levin A, Stevens L, McCullough PA. Cardiovascular disease and the kidney. Tracking a killer in chronic kidney disease. Postgrad Med. 2002;111:53–60
Al-Ahmad A, Levey A, Rand W et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001;38:955–62
Silverberg DS, Wexler D, Blum M et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function, functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000;35:1737–44
Silverberg DS, Wexler D, Iaina A. The importance of anemia and its correction in the management of severe congestive heart failure. Eur Heart Fail. 2002;4:681–6
Mayer G, Thum J, Cada EM et al. Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int. 1988;34:525–8
Painter P, Moore G, Carlson L et al. Effects of exercise training plus normalization of hematocrit on exercise capacity and health-related quality of life. Am J Kidney Dis. 2002;39:257–65
Fink J, Blahut S, Reddy M, Light P. Use of erythropoietin before the initiation of dialysis and its impact on mortality. Am J Kidney Dis. 2001;37:348–55
Collins AJ, Ma JZ, Xia A, Ebben J. Trends in anemia treatment with erythropoietin usage and patient outcomes. Am J Kidney Dis. 1998;32(Suppl. 4):5133–41
Collins AJ. Influence of target hemoglobin in dialysis patients on morbidity and mortality. Kidney Int. 2002; 80(Suppl.):44–8
Ofsthun N, Labrecque J, Lacson E, Keen M, Lazarus JM. The effects of higher hemoglobin levels on mortality and hospitalization in hemodialysis patients. Kidney Int. 2003;63:1908–14
Xue JL, St Peter WL, Ebben JP, Everson SE, Collins AJ. Anemia treatment in the pre-ESRD period and associated mortality in elderly patients. Am J Kidney Dis. 2002; 40:1153–61
Xia H, Ebben J, Ma JZ, Collins AJ. Hematocrit levels and hospitalization risks in hemodialysis. J Am Soc Nephrol. 1999;10:1309–16
Moreno F, Sanz-Guajardo D, López-Gómez JM, Jofre R, Valderrábano F. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients. Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology. J Am Soc Nephrol. 2000;11:335–42
Holland DC, Lam M. Predictors of hospitalization and death among pre-dialysis patients: a retrospective cohort study. Nephrol Dial Transplant. 2000;15:650–8
Revicki DA, Brown RE, Feeny DH et al. Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients. Am J Kidney Dis. 1995;25:548–54
Suzuki M, Tsutsui M, Yokogama A, Hirasawa Y. Normalization of hematocrit with recombinant human erythropoietin in chronic hemodialysis patients does not fully improve their exercise tolerance abilities. Artif Organs. 1995;19:1258–61
Pickett JL, Theberge DC, Brown WS et al. Normalizing hematocrit in dialysis function improves brain function. Am J Kidney Dis. 1999;33:1122–30
Valderrábano F, Jofre R, López-Gòmez JM. Quality of life in end-stage renal disease patients. Am J Kidney Dis. 2001;38:443–64.
Broom J. Anaemia in diabetic renal disease: an underestimated risk factor. Acta Diabetol. 2002;39(Suppl. 1):S2
Inomata S, Itoh M, Imai H, Sato T. Serum levels of erythropoietin as a novel marker reflecting the severity of diabetic nephropathy. Nephron. 1997;75:426–30
Ishimura E, Nishizawa Y, Okuno S et al. Diabetes mellitus increases the severity of anemia in non-dialyzed patients with renal failure. J Nephrol. 1998;11:83–6
Winkler AS, Marsden J, Chaudhuri KR, Hambley H, Watkins PJ. Erythropoietin depletion and anemia in diabetes mellitus. Diabet Med. 1999;16:813–19
Dikow R, Schwenger V, Schömig M, Ritz E. How should we manage anaemia in patients with diabetes? Nephrol Dial Transplant. 2002;17(Suppl. 1):67–72
Yun YS, Lee HC, Yoo NC et al. Reduced erythropoietin responsiveness to anemia in diabetic patients before advanced diabetic nephropathy. Diabet Res Clin Pract. 1999; 46:223–9
Cotroneo P, Ricerca M, Todaro L et al. Blunted erythropoietin response to anemia in patients with type 1 diabetes. Diabet Metab Res Rev. 2000;16:172–7
Kojima K, Totsuka Y. Anemia due to reduced serum erythropoietin concentration in nonuremic diabetic patients. Diabet Res Clin Pract. 1995;27:229–33
Vaziri ND, Kaupke CJ, Barton CH, Gonzaes E. Plasma concentration and the urinary excretion of erythropoietin in adult nephrotic syndrome. Am J Med. 1992; 92:35–40
Ishimitsu T, Ono H, Sugiyama M et al. Successful erythropoietin treatment for severe anemia in nephrotic syndrome without renal dysfunction. Nephron. 1996;74: 607–10
Bayés B, Serra A, Juncá J, Lauzurica R. Successful treatment of anemia of nephrotic syndrome with recombinant erythropoietin. Nephrol Dial Transplant. 1998;13:1894–5 (letter)
Bosman DR, Osborne CA, Mardsen JT, Macdougall IC, Gardner WN, Watkins PJ. Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure. Diabet Med. 2002;19:65–9
Qiao Q, Keinanen-Kiukaanniemi S, Laara E. The relationship between hemoglobin levels and diabetic retinopathy. J Clin Epidemiol. 1997;50:153–8
Aiello LP, Cahill MT, Wong JS. Systemic considerations in the management of diabetic retinopathy. Am J Ophthalmol. 2001;132:760–76
Friedman EA, Brown CD, Berman DH. Erythropoietin in diabetic macular edema and renal insufficiency. Am J Kidney Dis. 1995;26:202–8
Berman DH, Friedman EA. Partial absorption of hard exudates in patients with diabetic end-stage renal disease and severe anemia after treatment with erythropoietin. Retina. 1994;14:1–5
Priyadarshi A, Periyasamy S, Burke TJ et al. Effects of reduction of renal mass on renal oxygen tension and erythropoietin production in the rat. Kidney Int. 2002;61:542–6
Donnelly S. Why is erythropoietin made in the kidney? The kidney functions as a critmeter. Am J Kidney Dis. 2001;38:415–25
Norman JT, Clark IM, Garcia PL. Hypoxia promotes fibrogenesis in human renal fibroblasts. Kidney Int. 2000;58:2351–66
Eickelberg O, Seebach F, Riordan M et al. Functional activation of heat shock factor and hypoxia-inducible factor in the kidney. J Am Soc Nephrol. 2002;13:2094–101
Fine LG, Bandyopadhay D, Norman JT. Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. Kidney Int. 2000;57(Suppl. 75): S22–6.
Rosenberger C, Mandriota S, Jürgensen JS et al. Expression of hypoxia-inducible factor-1α and -2α in hypoxic and ischemic rat kidneys. J Am Soc Nephrol. 2002;13: 1721–32
Garcia DL, Anderson S, Rennke HG, Brenner BM. Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass. Proc Natl Acad Sci USA. 1988;85:6142–6
Bidani AK, Mitchell KD, Schwartz MM et al. Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model. Kidney Int. 1990;38:28–38
Eschbach JW, Kelly MR, Haley NR, Ables RI, Adamson JW. Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. N Engl J Med. 1989;321:158–63
Roth D, Smith RD, Schulman G et al. Effects of recombinant human erythropoietin on renal function in chronic renal failure predialysis patients. Am J Kidney Dis. 1994; 24:777–84
Kuriyama S, Tomonari H, Yoshida H et al. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron. 1997;77:176–85
Cody J, Daly C, Campbell M et al. Recombinant human erythropoietin for chronic renal failure anaemia in predialysis patients (Cochrane Review). In: The Cochrane Library, Issue 3,2002. Oxford: Update software
Fishbane S. Review: Recombinant erythropoietin decreases the need for blood transfusions and may delay dialysis in chronic renal failure. ACP J Club. 2002;136:85
Jungers P, Choukroun G, Oualim Z et al. Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients. Nephrol Dial Transplant. 2001;16:307–12
Hasslacher C, Schlueter V, Ruderich F, Koops S. Influence of anaemia on loss of kidney function of proteinuric type 1 and type 2 diabetic patients. Diabetologia. 2002;45(Suppl. 2):A363 (abstract)
Iseki K, Ikemiya Y, Iseki C, Takishita S. Haematocrit and the risk of developing end-stage renal disease. Nephrol Dial Transplant. 2003;18:899–905
Hörl WH. Oxidant Stress. Hagerstown: Lippincott, Williams & Wilkins, 2004 (In press)
Sommerburg O, Grune T, Hampl H. Does long-term treatment of renal anemia with recombinant erythropoietin influence oxidative stress in haemodialyzed patients. Nephrol Dial Transplant. 1998;13:2538–87
Klemm A, Voigt C, Friedrich M et al. Determination of erythrocyte antioxidant capacity in haemodialysis patients using electron paramagnetic resonance. Nephrol Dial Transplant. 2001;16:2166–71
Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res. 1999;31:261–72
Marui N, Offerman MK, Swerlick R et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993;92:1866–74
Parhami F, Fang ZT, Fogelman AM. Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. J Clin Invest. 1993;92:471–8
Fandrey J, Genius J. Reactive oxygen species as regulators of oxygen dependent gene expression. Adv Exp Med Biol. 2000;475:153–9
Sandau KB, Zhou J, Kietzmann T, Brüne B. Regulation of the hypoxia-inducible factor 1α by the inflammatory mediators nitric oxide and tumor necrosis factor-α in contrast to desferroxamine and phenylarsine oxide. J Bioc Chem. 2001;276:39805–11
Haddad JJ. Recombinant human interleukin (IL)- 1 betamediated regulation of hypoxia-inducible factor- 1 alpha (HIF- 1 alpha) stabilization, nuclear translocation and activation requires an antioxidant/reactive oxygen species (ROS)-sensitive mechanism. Eur Cytokine Netw. 2002; 13:250–60
Yang B, Johnson TS, Thomas GL et al. Expression of apoptosis-related genes and proteins in experimental chronic renal scarring. J Am Soc Nephrol. 2001;12:275–88
Kagedal K, Johansson U, Ollinger K. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J. 2001;15:1592–4
Yang B, Johnson TS, Thomas GL et al. Apoptosis and caspase-3 in experimental anti-glomerular basement membrane nephritis. J Am Soc Nephrol. 2001;12:485–95
Berns JS, Rudnick MR, Cohen RM, Bower JD, Wood BC. Effects of normal hematocrit on ambulatory blood pressure in epoetin-treated hemodialysis patients with cardiac disease. Kidney Int. 1999;56:253–60
Conlon PJ, Kovalik E, Schumm D, Minda S, Schwab SJ. Normalization of hematocrit in hemodialysis patients with cardiac disease does not increase blood pressure. Ren Fail. 2000;4:435–44
Paulitschke M, Ludat K, Riedel E, Hampl H. Long-term effects of rhuEPO therapy on erythrocyte rheology in dialysis patients with different target hematocrits. Clin Nephrol. 2000;53:536–41
Hörl WH, Jacobs C, Macdougall IC et al. European Best Practice Guidelines 17–18: Adverse effects. Nephrol Dial Transplant. 2000;15(Suppl. 4):51–6
Culp K, Flanigan M, Taylor L, Rothstein M. Vascular access thrombosis in new hemodialysis patients. Am J Kidney Dis. 1995;26:341–6
Wiesholzer M, Kitzwögerer M, Harm F et al. Prevalence of preterminal pulmonary thromboembolism among patients on maintenance hemodialysis treatment before and after introduction of recombinant erythropoietin. Am J Kidney Dis. 1999;33:702–8
Madore F, Lowrie EG, Brugnara C et al. Anemia in hemodialysis patients. Variables affecting this outcome predictor. J Am Soc Nephrol. 1997;8:1921–9
Ifudu O, Uribarri J, Rajwani I et al. Adequacy of dialysis and differences in hematocrit among dialysis facilities. Am J Kidney Dis. 2000;36:1166–74
Ifudu O. Evidence that adequacy of dialysis modulates uremic anemia. Nephron. 2001;88:1–5
Movilli E, Cancarini GC, Zani R et al. Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from use of biocompatible membranes in haemodialysis patients. Nephrol Dial Transplant. 2001; 16:111–14
Coladonato JA, Frankenfield DL, Reddan DN et al. Trends in anemia management among US hemodialysis patients. J Am Soc Nephrol. 2002;13:1288–95
Frankenfield D, Johnson CA, Wish JB, Rocco MV, Madore F, Owen WH Jr for the ESRP Core Indications Work Group. Anemia management of adult hemodialysis patients in the US: results from the 1997 ESRD core indicators project. Kidney Int. 2000;57:578–89
Ifudu O, Friedman EA. Effect of increased hemodialysis dose on endogenous erythropoietin production in end-stage renal disease. Nephron. 1998;79:50–4
Petronis KR, Carroll CE, Held PJ, Port FK. Effect of race on access to recombinant human erythropoietin in longterm hemodialysis patients. J Am Med Assoc. 1994; 271:1760–3.
Jansen MA, Hart AA, Korevaar JC, Dekker FW, Boeschoten EW, Krediet RT, NECOSAD Study Group. Predictors of the rate of decline of residual renal function in incident dialysis patients. Kidney Int. 2002;62:1046–53
Termorhuizen F, Korevaar JC, Dekker FW et al. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the Netherlands cooperative study on the adequacy of dialysis (Necosad). Am J Kidney Dis. 2003;41:1293–302
Wang AY, Wang M, Woo J et al. A novel association between residual renal function and left ventricular hypertrophy in peritoneal dialysis patients. Kidney Int. 2002; 62:639–47
House A, Pham B, Page DE. Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities. Nephrol Dial Transplant. 1998;13:1763–9
Locatelli F, Andrulli S, Pecchini F et al. Effect of high-flux dialysis on the anaemia of haemodialysis patients. Nephrol Dial Transplant. 2000;15:1399–409
Yamada S, Kataoka H, Kobayashi H, Ono T, Minakuchi J, Kawano Y. Identification of an erythropoietic inhibitor from the dialysate collected in the hemodialysis with PMMA membrane (BK-F). Contrib Nephrol. 1999;125:159–72
Vanholder R, De Smet R, Lameire N. Protein-bound uremic solutes: the forgotten toxins. Kidney Int. 2001;78:S266–70
Krieter DH, Canaud B. High permeability of dialysis membranes: what is the limit of albumin loss? Nephrol Dial Transplant. 2003;18:651–4
Macdougall IC. Role of uremic toxins in exacerbating anemia in renal failure. Kidney Int. 2001;59(Suppl. 78):S67–72
Bajo MA, Selgas R, Miranda B et al. Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity. Adv Pert Dial. 1991;7:296–300
Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients. Nephrol Dial Transplant. 2000;15:1207–11
Maduell F, del Pozo C, Garcia H et al. Change from conventional haemodiafiltration to on-line haemodiafiltration. Nephrol Dial Transplant. 1999;14:1202–7
Eiselt J, Racek J, Opatrny K Jr. The effect of hemodialysis and acetate-free biofiltration on anemia. Int J Artif Organs. 2000;23:173–80
Bonforte G, Grillo P, Zerbi S, Surian M. Improvement of anemia in hemodialysis patients treated by hemodiafiltration with high-volume on-line-prepared substitution fluid. Blood Purif. 2002;20:357–63
Lin CL, Huang CC, Yu CC et al. Improved iron utilization and reduced erythropoietin resistance by on-line hemodiafiltration. Blood Purif. 2002;20:349–56
Fagugli RM, Buoncristiani U, Ciao G. Anaemia and blood pressure correction obtained by daily haemodialysis induce a reduction of left ventricular hypertrophy in dialysed patients. Int J Artif Org. 1998;21:429–31
Woods JD, Port FK, Orzol S et al. Clinical and biochemical correlates of starting ‘daily’ hemodialysis. Kidney Int. 1999;55:2467–76
Lockridge RS, Anderson HK, Coffey LT et al. Nightly home hemodialysis in Lynchburgh, Virginia: economic and logistic considerations. Semin Dial. 1999;12:440–7
Klarenbach S, Heidenheim AP, Leitch R, Lindsay RM. The daily/nocturnal dialysis study group. Reduced requirement for erythropoietin with quotidian haemodialysis therapy. ASAIO J. 2002;48:57–61
Koury ST, Bondurant MS, Koury JM. Localization of erythropoietin synthesizing cells in murine kidney by in situ hybridization. Blood. 1988;71:524–37.
Dordal MS, Wang FF, Goldwasser E. The role of carbohydrate in erythropoietin action. Endocrinology. 1985; 116:2293–9
Cheetham JC, Smith DM, Aoki KH et al. NMR structure of human erythropoietin and a comparison with its receptor bound conformation. Nat Struct Biol. 1998;5:861–6
Syed RS, Reid SW, Li C et al. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature. 1998;395:511–16
Yamaguchi K, Akai K, Kawanishi G, Ueda M, Masuda S, Sasaki R. Effects of site-directed removal of N-glycosylation sites in human erythropoietin on its production and biological properties. J Biol Chem. 1991;266:20434–9
Takeuchi M, Takasaki S, Shimada M, Kobata R. Role of sugar chains in the in vitro biological activity of human erythropoietin produced in Chinese hamster ovary cell. J Biol Chem. 1990;265:12127–30
Wasley LC, Timony G, Murtha P et al. The importance of N- and O-linked oligosaccharides for the biosynthesis and in vitro and in vivo biologic activities of erythropoietin. Blood. 1991;77:2624–32
Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001;84(Suppl. 1):3–10
Macdougall IC, Roberts DE, Coles GA, Williams JD. Clinical pharmacokinetics of epoetin (recombinant human erythropoietin). Clin Pharmacokinet. 1991;20:99–113
Veng-Pedersen P, Widness JA, Pereira LM, Peters C, Schmidt RL, Lowe LS. Kinetic evaluation of nonlinear drug elemination by a disposition decomposition analysis. Application to the analysis of the nonlinear elimination kinetics of erythropoietin in adult humans. J Pharm Sci. 1995;84:760–7
Chapel SH, Veng-Pedersen P, Schmidt RL, Widness JA. Receptor-based model accounts for phlebotomy-induced changes in erythropoietin pharmacokinetics. Exp Hematol. 2001;29:425–31
Jelkmann W. The enigma of the metabolic fate of circulating erythropoietin (Epo) in view of the pharmacokinetics of the recombinant drugs rhEpo and NESP. Eur J Haematol. 2002;69:265–74
Sasaki H, Bothner B, Dell A, Fukuda M. Carbohydrate structure of erythropoietin expressed in Chinese hamster ovary cells by a human erythropoietin cDNA. J Biol Chem. 1987;262:12059–76
Skibeli V, Nissen-Lie G, Torjesen P. Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin. Blood. 2001;98:3626–34
Storring PL, Tiplady RJ, Gaines Das RE et al. Epoetin alfa and beta differ in their erythropoietin isoform composition and biological properties. Br J Haematol. 1998;100: 79–89
Toyoda T, Itai T, Arakawa T, Aoki K, Yamaguchi H. Stabilization of human recombinant erythropoietin through interactions with the highly branched N-glycans. J Biochem (Toyko). 2000;128:731–7
Stockenhuber F, Loibl U, Gottsauner-Wolf M et al. Pharmacokinetics and dose response after intravenous and subcutaneous administration of recombinant erythropoietin in patients on regular haemodialysis treatment or continuous ambulatory peritoneal dialysis. Nephron. 1991; 59:399–402
Nimtz M, Martin W, Wray V, Kloppel KD, Augustin J, Conradt H. Structures of sialylated oligosacharides of human erythropoietin expressed in recombinant BHK-21 cells. Eur J Biochem. 1993;213:39–56
Nimtz M, Wray V, Rudiger A, Conradt HS. Identification and structural characterization of a mannose-6-phosphate containing oligomannosidic N-glycan from human erythropoietin secreted by recombinant BHK-21 cells. FEBS Lett. 1995;365:203–8
Macdougall IC, Gray SJ, Elston O et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol. 1999; 10:2392–5
Allon M, Kleinman K, Walczyk M et al. Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis. Clin Pharmacol Ther. 2002;72: 546–55
Muirhead N, Churchill DN, Goldstein M et al. Comparison of subcutaneous and intravenous recombinant human erythropoietin for anemia in hemodialysis patients with significant comorbid disease. Am J Nephrol. 1992;12: 303–10
Schaller R, Sperschneider H, Thieler H et al. Differences in intravenous and subcutaneous application of recombinant human erythropoietin: a multicenter trial. Artif Organs. 1994;18:552–8
Albitar S, Meulders Q, Hammoud H et al. Subcutaneous versus intravenous administration of erythropoietin improves its efficiency for the treatment of anaemia in haemodialysis patients. Nephrol Dial Transplant. 1995; 10(Suppl. 6):40–3
Canaud BC, Bennhold I, Delon S et al. What is the optimum frequency of administration of r-HuEPO for correcting anemia in hemodialysis patients? Dial Transplant. 1995; 24:306–29
Virot JS, Janin G, Guillaumie J et al. Must erythropoietin be injected by the subcutaneous route for every hemodialyzed patient? Am J Kidney Dis. 1996;28:400–8
Kaufman JS, Reda DJ, Fye CL et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med. 1998;339:578–83
Vanrenterghem Y, Barany P, Mann JF et al. Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequencey compared with rHuEPO in dialysis patients. Kidney Int. 2002;62:2167–75
Salmonson P. Pharmacokinetic and pharmacodynamic studies on recombinant human erythropoietin. Scand J Urol Nephrol Suppl. 1990;129:1–6
Macdougall IC, Roberts DE, Coles GA, Williams JD. Clinical pharmacokinetics of epoetin (recombinant human erythropoietin). Clin Pharmacokinet. 1991;20:99–113
Besarab A, Reyes CM, Hornberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40:439–46
Jacobs C, Hörl WH, Macdougall IC et al. European Best Practice Guidelines 9–13; anaemia management. Nephrol Dial Transplant. 2000;15(Suppl. 4):33–42
McClellan WM, Frankenfield DL, Wish JB et al. End-Stage Renal Disease Core Indicators Work Group. Subcutaneous erythropoietin results in lower dose and equivalent hematocrit levels among adult hemodialysis patients: results from the 1998 End-stage Renal Disease Core Indicators Project. Am J Kidney Dis. 2001;37:E36
Taylor JE, Belch JJ, Fleming LW et al. Erythropoietin response and route of administration. Clin Nephrol. 1994;41: 297–302
Sunder-Plassmann G, Hörl WH. Importance of iron supply for erythropoietin therapy. Nephrol Dial Transplant. 1995;10:2070–6
De Schoenmakere G, Lameire N, Dhondt A et al. The haematopoietic effect of recombinant human erythropoietin in haemodialysis is independent of the mode of administration (iv. or s.c.). Nephrol Dial Transplant. 1998;13: 1770–5
Weiss LG, Clyne N, Fihlho JD et al. The efficacy of once weekly compared with two or three times weekly subcutaneous epotin β: results from a randomized controlled multicentre trial. Nephrol Dial Transplant. 2000;15: 2014–19
Locatelli F, Baldamus CA, Villa G, Ganea A, Martin de Francisco AL. One-weekly compared with three-times weekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeutic-equivalence study. Am J Kidney Dis. 2002;40:119–25
Eschbach JW. Treatment of anemia of chronic kidney disease. Am J Kidney Dis. 2001;37:191–4
Yu AW, Leung CB, Li PK, Lui SF, Lai KN. Pain perception following subcutaneous injections of citrate-buffered and phosphate-buffered epoetin alpha. Int J Artif Organs. 1998; 21:341–3
Veys N, Dhondt A, Lameire N. Pain at the injection site of subcutaneously administered erythropoietin: phosphatebuffered epoetin alpha compared to citrate-buffered epoetin alpha and epoetin beta. Clin Nephrol. 1998;49:41–4
St Peter WL, Lewis MJ, Macres MG. Pain comparison after subcutaneous administration of single-dose formulation versus multidose formulation of epogen in hemodialysis patients. Am J Kidney Dis. 1998;32:470–4
Besarab A. Physiological and pharmacodynamic considerations for route of EPO administration. Semin Nephrol. 2000;20:364–74
Besarab A, Flaharty KK, Erslev AJ et al. Clinical pharmacology and economics of recombinant erythropoietin in endstage renal disease: the case for subcutaneous administration. J Am Soc Nephrol. 1992;2:1405–16.
Cheung W, Minton N, Gunawardena K. Pharmacokinetics and pharmacodynamics of epoetin alfa once weekly and three times weekly. Eur J Clin Pharmacol. 2001;57:411–18.
Piccoli A, Malagoli A, Komninos G, Pastor G. Subcutaneous epoetin-alpha every one, two and three weeks in renal anemia. J Nephrol. 2002;15:565–74.
Grzeszczak W, Sulowicz W, Rutowski B et al., on behalf of the European Collaborative Group. Once weekly and once fortnightly (every two weeks) subcutaneous epoetin beta is effective in PD patients with chronic renal anaemia. Nephrol Dial Transplant. 2002;17(Suppl. 1):24 (abstract 076).
Acharya VN, Sinha DK, Almeida AF, Pathare AV. Effect of low dose recombinant human omega erythropoietin (rHuEPO) on anaemia in patients on hemodialysis. J Assoc Phys India. 1995;43:539–42.
Sikole A, Spasovski G, Zafirov D, Polenakovic M. Epoetin omega for treatment of anemia in maintenance hemodialysis patients. Clin Nephrol. 2002;57:237–45.
Bren A, Kandus A, Varl J et al. A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialyisis patients: a prospective, controlled crossover study. Artif Organs. 2002;26:91–7.
Milutinovic S, Plavljanic D, Orsanic D. Once weekly erythropoietin omega is safe and effective in treatment of anemia in dialysis patients. J Am Soc Nephrol. 2002;13:463A (abstract).
Locatelli F, Olivares J, Walker R, Wilkie M and the European/Australian NESP 980202 Study Group. Novel erythropoiesis stimulating protein (NESP) administered subcutaneously corrects anemia in subjects with chronic renal insufficiency (CRI) when administered at a reduced dose frequency compared with recombinant-human erythropoietin (r-HuEPO). J Am Soc Nephrol. 2000;11:A1486 (abstract).
Macdougall IC, Matcham J, Gray SJ. Correction of anaemia with darbepoetin alpha in patients with chronic kidney disease receiving dialysis. Nephrol Dial Transplant. 2003; 18:576–81.
Aljama P, Bommer J, Canaud B et al. Practical guidelines for the use of NESP in treating renal anaemia. Nephrol Dial Transplant. 2001;16 (Suppl. 3):22–8.
Nissenson AR, Swan SK, Lindberg JS et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002; 40:110–18.
Nissenson AR, Swan SK, Lindberg JS et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002; 40:110–18.
Hörl WH, Holzer H, Mayer GJ. Behandlung der renalen Anämie mit Darbepoetin alfa — Ergebnisse einer österreichischen Multicenter-Studie. Wien Klin Wochenschr. 2002; 114:967–71.
Nissenson AR. Dosing darbepoetin alfa. Am J Kidney Dis. 2002;40:872 (letter).
Scott SD. Dose conversion from recombinant human erythropoietin to darbepoetin alfa: recommendations from clinical studies. Pharmacotherapy. 2002;22:160–5S.
Cheung WK, Goon BL, Guilfoyle MC, Wacholtz MC. Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects. Clin Pharmacol Ther. 1998;64: 412–23.
Eschbach JW, Abdulhadi MH, Browne JK et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann Intern Med. 1989;111:992–1000.
Walker R, on behalf of the European/Australian 20000144 Study Group. AranespTM (Darbepoetin alfa) administered at a reduced frequency of once every 4 weeks (Q4W) maintains hemoglobin levels in patients with chronic kidney disease (CKD) receiving dialysis. Am J Kidney Dis. 2002;39:A33 (abstract).
Sunder-Plassmann G, Hörl WH. Erythropoietin and iron. Clin Nephrol. 1997;47:141–57.
Macdougall IC, Cavill I, Hulme B et al. Detection of functional iron deficiency during erythropoietin treatment: a new approach. Br Med J. 1992;304:225–6.
Braun J, Lindner K, Schreiber M, Heidler A, Hörl WH. Percentage of hypochromic red cells as predictor of erythropoietic and iron response after iv. iron supplementation in maintenance haemodialysis patients. Nephrol Dial Transplant. 1997;12:1173–81
Cullen P, Söffker J, Höpfl M et al. Hypochromic red cells and reticulocyte haemoglobin content as markers of irondeficient erythropoiesis in patients undergoing chronic haemodialysis. Nephrol Dial Transplant. 1999;14:659–65
Jones CH, Richardson D, Ayers S, Newstaed CG, Will EJ, Davison AM. Percentage hypochromic red cells and the response to intravenous iron therapy in anaemic haemodialysis patients. Nephrol Dial Transplant. 1998;13:2873–6
Tessitore N, Solero GP, Lippi G et al. The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin. Nephrol Dial Transplant. 2001;16:1416–23
Lorenz M, Kletzmayr J, Perschl A, Furrer A, Hörl WH, Sunder-Plassmann G. Anemia and iron deficiency in longterm renal transplant patients. J Am Soc Nephrol. 2002; 13:794–7
Bovy C, Tsobo C, Crapanzano L et al. Factors determining the percentage of hypochromic red blood cells in hemodialysis patients. Kidney Int. 1999;56:1113–19.
Fishbane S, Shapiro W, Dutka P, Valenzuela OF, Faubert J. A randomized trial of iron deficiency testing strategies in hemodialyis patients. Kidney Int. 2001;60: 2405–11
Besarab A. Evaluating iron sufficiency: a clearer view. Kidney Int. 2001;60:2412–14
Chuang C-L, Liu R-S, Wie Y-H, Huang T-P, Tarng D-C. Early prediction of response to intravenous iron supplementation by reticulocyte haemoglobin content and highfluorescence reticulocyte count in haemodialysis patients. Nephrol Dial Transplant. 2003;18:370–7
Baynes RD. Refining the assessment of body iron status. Am J Clin Nutr. 1996;64:793–4
Cook JD, Skikne BS, Baynes RD. Serum transferrin receptor. Annu Rev Med. 1993;44:63–74
Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med. 1992;119:385–90
Cooper MJ, Zlotkin SH. Day-to-day variation of transferrin receptor and ferritin in healthy men and women. Am J Clin Nutr. 1996;64:738–42
Eschbach JW, Haley NR, Egrie JC, Adamson JW. A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects. Kidney Int. 1992;42:407–16
Sunder-Plassmann G, Spitzauer S, Hörl WH. The dilemma of evaluating iron status in dialysis patients. Limitations of available diagnostic procedures. Nephrol Dial Transplant. 1997;12:1575–80
Weiss G, Houston T, Kastner S, Jöhrer K, Grünewald K, Brock JH. Regulation of cellular iron metabolism by erythropoietin: activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells. Blood. 1997;89:680–7
Huebers HA, Beguin Y, Pootrakul P, Einspahr D, Finch CA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood. 1990; 75:102–7
Beguin Y, Clemons GK, Pootrakul P, Fillet C. Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin. Blood. 1993;81:1067–76
Ponka P. Tissue-specific regulation of iron metabolism and heme synthesis: distinct control mechanisms in erythroid cells. Blood. 1997;89:1–25
Drüeke TB, Barany P, Cazzola M et al. Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin-treated patients. Clin Nephrol. 1997;48:1–8
Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89:1052–7
Chiang WC, Tsai TJ, Chen YM, Lin SL, Hsieh BS. Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients. Clin Nephrol. 2002;58:363–9
Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood. 2002 (www.bloodjournal.org)
NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease. Update 2000. III. Iron Support. Am J Kidney Dis. 2001;37(Suppl. 1):S194–206
Hsu CY, McCulloch CE, Curhan GC. Iron status and hemoglobin level in chronic renal insufficiency. J Am Soc Nephrol. 2002;13:2783–6
Hudson JQ, Comstock TJ. Consideration for optimal iron use for anemia due to chronic kidney disease. Clin Ther. 2001;23:1637–71.
Kooistra MP, Niemantsverdriet EC, van Es AD, Mol Beermann NM, Struyvenberg A, Marx JJM. Iron absorption in erythropoietin-treated haemodialysis patients: effects of iron availability, inflammation and aluminium. Nephrol Dial Transplant. 1998;13:82–8
Kooistra MP, Marx JJM. The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients. Nephrol Dial Transplant. 1998;13: 2578–82
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;16:967–74
Trivedi HS, Brooks BJ. Erythropoietin therapy in predialysis patients with chronic renal failure: lack of need for parenteral iron. Am J Nephrol. 2003;23:78–85
Dittrich E, Puttinger H, Schneider B, Hörl WH, Haag Weber M, Vychytil A. Is absorption of high-dose oral iron sufficient in peritoneal dialysis patients? Pert Dial Int. 2000;20:667–73
Ahsan N. Intravenous infusion of total dose iron is superior to oral in treatment of anemia in peritoneal dialysis patients: a single centre comparative study. J Am Soc Nephrol. 1998;9:664–8
Hörl WH, Dreyling K, Steinhauer HB, Engelhardt R, Schollmeyer P. Iron status of dialysis patients under rhuEPO therapy. Contrib Nephrol. 1990;87:78–86
Allegra V, Mengozzi G, Vasile A. Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. Nephron. 1991;57:175–82
Bergmann M, Grützmacher P, Heuser J, Kaltwasser JP. Iron metabolism under rhEPO therapy in patients on maintenance hemodialysis. Int J Artif Organs. 1990;13: 109–12
Kooistra MP, van Es A, Struyvenberg A, Marx JJM. Iron metabolism in patients with the anemia of end-stage renal disease during treatment with recombinant human erythropoietin. Br J Haematol. 1991;79:634–9
Anastassiades EG, Horwarth G, Horwarth J et al. Monitoring of iron requirements in renal patients on erythropoietin. Nephrol Dial Transplant. 1993;8:846–53
Dunea G, Swagel MA, Bodiwala U, Arruda JAL. Intradialytic oral iron therapy. Int J Artif Organs. 1994;17:261–4
Wingard RL, Parker RA, Ismail N, Hakim RM. Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin. Am J Kidney Dis. 1995;25:433–9
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;26:41–6
Silverberg DS, Iaina A, Peer G et al. 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;27:234–8
Macdougall IC, Tucker B, Thompson J, Tomson CRV, Baker LRI, Raine AEG. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int. 1996;50:1694–9
Bailie GR, Johnson CA, Mason NA. Parenteral iron use in the management of anemia in end-stage renal disease patients. Am J Kidney Dis. 2000;35:1–12
Macdougall IC. Intravenous administration of iron in epoetin-treated haemodialysis patients — which drugs, which regimen? Nephrol Dial Transplant. 2000;15:1743–5
Jayakumar S, Jayakumar SA. Iron dextran anaphylactic-like reaction after a negative test dose and subsequent successful administration of three doses. Dial Transplant. 2000;29: 198–201.
Fletes R, Lazarus JM, Gag J, Chertow GM. Suspected iron dextran-related adverse drug events in hemodialysis patients. Am J Kidney Dis. 2001;37:743–9
Van Wyck DB, Cavallo G, Spinowitz BS et al. Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial. Am J Kidney Dis. 2000;36: 88–97
Yee J, Besarab A. Iron sucrose: the oldest iron therapy becomes new. Am J Kidney Dis. 2000;40:1111–21
Prakash S, Walele A, Dimkovic N, Bargman J, Vas S, Oreopoulos D. Experience with a large dose (500 mg) of iv dextran and saccharate in peritoneal dialysis patients. Perit Dial Int. 2001;21:290–5
Chandler G, Harchowal J, Macdougall IC. Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis. 2001;38:988–91
Aggarwal HK, Tziviskou E, Bellizzi V et al. Prolonged administration over six hours of large doses of intravenous iron saccharate (500 mg) prevents severe adverse reactions in peritoneal dialysis patients. Pert Dial Int. 2002;22:636–7
Faich G, Strobos J. Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextran. Am J Kidney Dis. 1999;33:464–70
Eschbach JW, Strobos J. Sodium ferric gluconate complex (FerrlecitR): prospective experience in 1122 hemodialysis patients. J Am Soc Nephrol. 2000;11:249A
Coyne DA, Adkinson NF, Nissenson AR et al. Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions iron dextran-sensitive and dextran-tolerant patients. Kidney Int. 2003;63:217–24
Folkert VW, Mchael B, Agarwal R et al. Ferrlecit Publication Committee. Chronic use of sodium ferric gluconate complex in hemodialysis patients: safety of higher-dose (> or = 250 mg) administration. Am J Kidney Dis. 2003;41:651–7
Michelis R, Gery R, Sela S et al. Carbonyl stress induced by intravenous iron during haemodialysis. Nephrol Dial Transplant. 2003;18:924–30
Deicher R, Ziai F, Cohen G, Mülllner M, Hörl WH. Highdose parenteral iron sucrose depresses neutrophil intracellular killing capacity. Kidney Int. 2003;64:728–36
Sengölge G, Kletzmayr J, Ferrara I, Perschl A, Hörl WH, Sunder-Plassmann G. Impairment of transendothelial leukocyte migration by iron complexes. J Am Soc Nephrol. 2003;14:2639–44
Kosch M, Bahner U, Bettger H, Matzkies F, Teschner M, Schaefer RM. A randomized, controlled parallel-group trial an efficacy and safety of iron sucrose (VenoferR) vs. iron gluconate (FerrlecetinR) in haemodialysis patients treated with rHuEpo. Nephrol Dial Transplant. 2001;16:1239–44
Richardson D, Bartlett C, Jolly H, Will EJ. Intravenous iron for CAPD populations: proactive or reactive strategies? Nephrol Dial Transplant. 2001;16:115–19
Dittrich E, Schillinger M, Sunder-Plassmann G, Hörl WH, Vychytil A. Efficacy of low-dose intravenous iron sucrose regimen in peritoneal dialysis patients. Pert Dial Int. 2002;22:60–6
Hörl WH. Should we still use iron dextran in hemodialysis patients? Am J Kidney Dis. 2001;27:859–61
Patruta SI, Edlinger R, Sunder-Plassmann G, Hörl WH. Neutrophil impairment associated with iron therapy in hemodialysis patients with functional iron deficiency. J Am Soc Nephrol. 1998;9:655–63
Kletzmayr J, Hörl WH. Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant. 2002;17(Suppl. 2):25–9
Sullivan JL. Iron and the sex differences in heart disease risk. Lancet. 1981;1:1293–4.
Meyers DG, Strickland D, Maloley PA, Seburg JK, Wilson JE, McManus BF. Possible association of a reduction in cardiovascular events with blood donation. Heart. 1997;78:188–93
Salonen JT, Tuomainen TP, Salonen R, Lakka TA, Nyyssönen K. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Epidemiol. 1998;148: 445–51
Ascherio A, Rimm EB, Giovannucci E, Willet WC, Stampfer MJ. Blood donation and risk of coronary heart disease in men. Circulation. 2001;103:52–7
Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation. 1997;96:3300–7
Tuomainen TP, Punnonen K, Nyyssönen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation. 1998; 97:1461–6
Klipstein-Grobusch K, Koster JF, Grobbee DE et al. Serum ferritin and risk of acute myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr. 1999;69:1231–6
Lee FY, Lee TS, Pan CC et al. Colocalization of iron and ceroid in human atherosclerosis lesions. Atherosclerosis. 1998;138:281–8
Kuryshev YA, Brittenham GM, Fujioka H et al. Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease. Circulation. 1999;100:675–83
Bartfay WJ, Butany J, Lehotay DC et al. A biochemical, histochemical and electron microscopic study on the effects of iron-loading on the hearts of mice. Cardiovasc Pathol. 1999;8:305–14
Link G, Konijn AM, Hershko C. Cardioprotective effects of alpha-tocopherol, ascorbate, deferoxamine, and deferiprone: mitochondrial function in cultured, iron-loaded heart cells. J Lab Clin Med. 1999;133:179–88
Roob JM, Khoschsorur G, Tiran A et al. Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol. 2000;11:539–49
Kirk EA, Heinecke JW, Le Boeuf RC. Iron overload diminishes atherosclerosis in apoE-deficient mice. J Clin Invest. 2001;107:1545–53
Drüeke T, Witko-Sarsat V, Ziad M et al. Iron therapy, and advanced oxidation protein products and carotid artery intima-media thickness in end-stage renal disease. Circulation. 2002;106:2212–17
Tovbin D, Mazor D, Vorobiov M, Chaimovitz C, Meyerstein N. Induction of protein oxidation by intravenous iron in hemodialysis patients: role of inflammation. Am J Kidney Dis. 2002;40:1005–12
Kalantar-Zadeh K, Rodriguez R, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis. 2001;37:564–72
Kletzmayr J, Hörl WH. Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant. 2002;17(Suppl. 2):27–32
Feldman HI, Santanna J, Guo W et al. Iron administration and clinical outcomes in hemodialysis patients. J Am Soc Nephrol. 2002;13:734–44
Födinger M. Sunder-Plassmann G. Inherited disorders of iron metabolism. Kidney Int. 1999;55(Suppl. 69):S22–34
Roest M, van der Schouw YT, de Valk B et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular mortality in women. Circulation. 1999;100:1268–73.
Tuomainen TP, Kontula K, Nyyssönen K et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation. 1999;100: 1274–9
Sullivan JL. Iron and the genetics of cardiovascular disease. Circulation. 1999;100:1260–3
Rossi E, McQuillan BM, Hung J et al. Serum ferritin and C282Y mutation of the hemochromatosis gene as predictors of asymptomatic carotid atherosclerosis in a community population. Stroke. 2000;31:3015–20
Franco RF, Zago MA, Trip MD et al. Prevalence of hereditary hemachromatosis in premature atherosclerotic vascular disease. Br J Haematol. 1998;102:1172–5
Hetet G, Elbaz A, Gariepy J et al. Association studies between hemochromatosis gene mutations and the risk of cardiovascular diseases. Eur J Clin Invest. 2001;31: 382–8
Bosio S, De Gobbi M, Roetto A et al. Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations. Blood. 2002;100:2246–8
Sullivan JL, Zacharski LR. Hereditary haemachromatosis and the hypothesis that iron depletion protects against ischemic heart disease. Eur J Clin Invest. 2001;31:375–7
Salonen JT, Korpela H, Nyyssönen K et al. Association of body iron stores and the risk of acute myocardial infarction in men. Circulation. 1998;97:1461–6
Duffy SJ, Biegelsen ES, Holbrook M et al. Iron chelation improves endothelial function in patients with coronary artery disease. Circulation. 2001;103:2799–804
Pietrangelo A. Physiology of iron transport and the hemochromatosis gene. Am J Physiol Gastrintest Liver Physiol. 2002;282:G304–414
Fillebeen C, Pantopoulos K. Redox control of iron regulatory proteins. Redox Rep. 2002;7:15–25
Kim HJ, Kim SG. Alterations in cellular Ca2+ and free iron pool by sulfur amino acid deprivation: the role of ferritin light chain downregulation in prooxidant production. Biochem Pharmacol. 2002;63:647–57
Comporti M, Signorini C, Buonocore G, Ciccoli L. Iron release, oxidative stress and erythrocyte aging. Free Radic Biol Med. 2002;32:568–76
Sommerburg O, Grune T, Hampl H et al. Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in hemodialysed patients? Nephrol Dial Transplant. 1998;15:1743–5
Wang Q, Doerschuk CM. Neutrophil-induced changes in the biomechanical properties of endothelial cells: roles of ICAM-1 and reactive oxygen species. J Immunol. 2000;164: 6487–94
Simonart T, Degraef C, Stordeur P et al. Iron induces Bc-2 expression in human dermal microvascular endothelial cells. Free Radic Res. 2001;34:221–35
Simonart T, Degraef C, Andrei G et al. Iron chelators inhibit the growth and induce the apoptosis of Kaposi ’s sarcoma cells and of their putative endothelial precursors. J Invest Dermatol. 2000;115:893–900
Tampo Y, Kotamraju S, Chitambar CR et al. Oxidative stress-induced iron signaling is responsible for peroxidedependent oxidation of dichlorodihydrofluorescein in endothelial cells: role of transferrin receptor-dependent iron uptake in apoptosis. Circ Res. 2003;92:56–63
Koo SW, Casper KA, Otto KB, Gira AK, Swerlick RA. Iron chelators inhibit VCAM-1 expression in human dermal microvascular endothelial cells. J Invest Dermatol. 2003;120: 871–9
Balla J, Vercellotti GM, Nath K et al. Haem, haem oxygenase and ferritin in vascular endothelial cell injury. Nephrol Dial Transplant. 2003;18(Suppl. 5):8–12.
Visseren FL, Verkerk MS, van der Bruggen T, Marx JJ, van Asbeck BS, Diepersloot RJ. Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A. Eur J Clin Invest. 2002;32(Suppl. 1):84–90
Zager RA, Johnson AC, Hanson SY, Wasse H. Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis. 2002; 40:90–103
Zhou Xi, Laszik Z, Wang XQ, Silva FG, Vaziri ND. Association of renal injury with increased oxygen free radical activity and altered nitric oxide metabolism in chronic experimental hemosiderosis. Lab Invest. 2000;80:1905–14
Hershko C. Iron and infection. In: Hallberg LAG, editor. Iron Nutrition in Health and Disease. New York: John Libbey, 1996:231–8
Olynyk JK, Clarke SL. Iron overload impairs pro-inflammatory cytokine responses by Kupffer cells. J Gastroenterol Hepatol. 2001;16:438–44
Nishiya K, Wang H, Tahara K, Hashimoto K. Enhancement by iron of interleukin 1 induced granulocyte macrophage colony stimulating factor (GM-CSF) production by human synovial fibroblasts. Ann Rheum Dis. 2003;62:89–90
Weiss G, Meusburger E, Radacher G, Garimorth K, Neyer U, Mayer G. Effect of iron treatment on circulating cytokine levels in ESRD patients receiving recombinant human erythropoietin. Kidney Int. 2003;64:572–8
Oexle H, Kaser A, Most J et al. Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells. J Leukoc Biol. 2003;74:287–94
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
Zingraff J, Drüeke T, Marie P, Man NK, Jungers P, Bordier P. Anemia and secondary hyperparathyroidism. Arch Intern Med. 1978;138:1650–2
Barbour GL. Effect of parathyroidectomy on anemia in chronic renal failure. Arch Intern Med. 1979;139:889–91
Drüeke TB, Eckardt KU. Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients. Nephrol Dial Transplant. 2002;17(Suppl. 5):28–31
Yasunaga C, Matsuo K, Yanaigida T, Matsuo S, Nakamoto M, Goya T. Early effects of parathyroidectomy on erythropoietin production in secondary hyperparathyroidism. Am J Surg. 2002;183:199–204
Meytes D, Bogin E, Ma A, Dukes PP, Massry SG. Effect of parathyroid hormone on erythropoiesis. J Clin Invest. 1981; 67:1263–9
McGonigle RJS, Wallin JD, Husserl F et al. Potential role of parathyroid hormone as an inhibitor of erythropoiesis in the anemia of renal failure. J Lab Clin Med. 1984;104:1016–26
Argiles A, Lorho R, Mourad G, Mion CM. High-dose alfacalcidol for anaemia in dialysis [letter]. Lancet. 1993;342:378–9
Albitar S, Genin R, Fen-Chong M, Serveaux MO, Schohn D, Chuet C. High-dose alfacalcidol improves anaemia in patients on haemodialyis. Nephrol Dial Transplant. 1997;12:514–18
Carozzi, S, Ramello A, Nasini MG et al. Ca and 1,25(OH)2D3 regulate in vitro and in vivo the response to human recombinant erythropoietin in CAPD patients. Adv Pert Dial. 1990;6:312–15
Sitrin MD, Bissonnette M, Bolt MJ et al. Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells. Steroids. 1999;64:137–42
Kurella M, Butterly DW, Smith SR. Post transplant erythrocytes in hypercalcemic renal transplant recipients. Am J Transplant. 2003;3:873–7
Aucella F, Gatta G, Vigilante M et al. Calcitriol increases burst forming unit-erythroid (BFU-E) in vitro proliferation in chronic uremia. Synergic effect with DNA recombinant erythropoietin (rHu-Epo). Minerva Urol Nefrol. 2001;53:1–5
Alon DB, Chaimovitz C, Dvilansky A et al. Novel role of 1,25(OH)2D3 in induction of erythroid progenitor cell proliferation. Exp Hematol. 2002;30:403–9
Christ ER, Cummings MH, Westwood NB et al. The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. J Clin Endocrinol Metab. 1997;82:2985–90
Sohmiya M, Kato Y. Effect of long-term administration of recombinant human growth hormone (rhGH) on plasma erythropoietin (EPO) and hemoglobin levels in anaemic patients with adult GH deficiency. Clin Endocrinol. 2001;55:749–54
Iglesias P, Diez JJ, Fernandex-Reyes MJF et al. Recombinant human growth hormone therapy in malnourished dialysis patients: a randomized trial. Am J Kidney Dis. 1998;32:454–63
Johannsson G, Bengtsson BA, Ahlmen J. Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement. Am J Kidney Dis. 1999;33:709–17
Sohmiya M, Ishikawa K, Kato Y. Stimulation of erythropoietin secretion by continuous subcutaneous infusion of recombinant human GH in anemic patients with chronic renal failure. Eur J Endocrinol. 1998;138:302–6
Deicher R, Hörl WH. Anemia as a risk factor for the progression of chronic kidney disease. Curr Opin Nephrol Hypertens. 2003;12:139–43
Fisher J. Erythropoietin: physiology and pharmacology update. Exp Biol Med. 2003;228:1–14
Powell DR, Rosenfeld RG, Baker BK, Liu F, Hintz RL. Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor-I (IGF-I) and IGF-II in acid-chromatographed uremic serum. J Clin Endocrinol Metab. 1986;63:1186–92
Goldberg AC, Trivedi B, Delmez JA, Harter HR, Daughaday WH. Uremia reduces serum insulin-like growth factor I, increases insulin like growth factor II, and modifies their serum protein binding. J Clin Endocrinol Metab. 1982;55:1040–5
Shih LY, Huang JY, Lee CT. Insulin-like growth factor I plays a role in regulating erythropoiesis in patients with endstage renal disease and erythrocytosis. J Am Soc Nephrol. 1999;10:315–22
Urena P, Bonnardeaux A, Eckardt KU, Kurtz A, Drüeke TB. Insulin-like growth factor I: a modulator of erythropoiesis in uremic patients? Nephrol Dial Transplant. 1992;7:40–4
Rajaram S, Baylink DJ, Mohan S. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocrinol Rev. 1997;18: 801–31
Phillips LS, Fusco AC, Unterman TG, del Greco F. Somatomedin inhibitor in uremia. J Clin Endocrinol Metab. 1984;59:764–74
Powell D, Rosenfeld R, Sperry J, Baker B, Hintz R. Serum concentration of insulin-like growth factor (IGF)-I, IGF-II and unsaturated somatomedin carrier proteins in children with chronic renal failure. Am J Kidney Dis. 1987;10: 287–92
Brox AG, Zhang F, Guyda H, Gagnon RF. Subtherapeutic erythropoietin and insulin-like growth factor-1 correct the anemia of chronic renal failure in the mouse. Kidney Int. 1996;50:937–43
Miyagawa SH, Kobayashi M, Konishi N, Sato T, Ueda K. Insulin and insulin-like growth factor I support the proliferation of erythroid progenitor cells in bone marrow through the sharing of receptors. Br J Haematol. 2000;109:555–62
Deicher R, Hörl WH. Hormonal adjuvants for the treatment of renal anemia. Eur J Clin Invest. 2004 (In press)
Teruel J, Marcen R, Navarro J et al. Evolution of serum erythropoietin after androgen administration to hemodialysis patients. A prospective study. Nephron. 1995;70: 282–6
Neff M, Goldberg J, Slifkin R et al. A comparison of androgens for anemia in patients on hemodialysis. N Engl J Med. 1981;304:871–5
Parker PA, Izard MW, Maher JF. Therapy of iron deficiency in patients on maintenance dialysis. Nephron. 1979;23: 181–6
Solomon LR, Hendler ED. Prospective controlled study of androgen therapy in the anemia of chronic renal disease: effects on iron kinetics. Acta Haematol. 1988;79:12–19
Navarro JF, Mora C, Macia M, Garcia J. Randomized prospective comparison between erythropoietin and androgens in CAPD patients. Kidney Int. 2002;61:1537–44
Hagenfeldt Y, Linde K, Sjoberg HE, Zumkeller W, Arver S. Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I (IGF-1) in hypogonadal men. Int J Androl. 1992;15:93–102
Hobbs CJ, Plymate SR, Rosen CJ, Adler RA. Testosterone administration increases insulin-like-growth factor-I levels in normal men. J Clin Endocrinol Metab. 1993;77:776–9
Ballal SH, Domoto DT, Polack DC, Mardciulonis 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
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
Berns 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
Teruel JL, Marcen R, Navarro-Antolin J, Aguilera A, Fernandez-Juarez G, Ortuno J. Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study. J Am Soc Nephrol. 1996;7:140–4
Teruel J, Marcen R, Navarro J et al. Evolution of serum erythropoietin after androgen administration to hemodialysis patients. A prospective study. Nephron. 1995;70: 282–6
Johansen KL, Mulligan K, Schambelan M. Anabolic effects of nandrolone decanoate in patients receiving dialysis. J Am Med Assoc. 1998;281:1275–81
Johansen KL. The role of nandrolone decanoate in patients with end stage renal disease in the erythropoietin era. Int J Artif Organs. 2001;24:183–5
Teruel JL, Lasuncion MA, Rivera M et al. Nandrolone decanoate reduces serum lipoprotein(a) concentration in hemodialysis patients. Am J Kidney Dis. 1997;29:569–75
Hsu CY, Bates DW, Kuperman GJ, Curhan GG. Relationship between hematocrit and renal function in men and women. Kidney Int. 2001;59:725–31
Jungers P-Y, Robino C, Choukroun G, Nguyen-Khoa N, Massy ZA, Jungers P. Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients. Nephrol Dial Transplant. 2002;17:1621–7
Duncan JA, Levin A. Sex, hemoglobin and kidney disease: new perspectives. Eur J Clin Invest. 2004 (In press)
European best practice guidelines for the management of anaemia in patients with chronic renal failure. Working Party for European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant. 1999;14(Suppl. 5):1–50
Hörl WH. Is there a role for adjuvant therapy in patients being treated with epoetin? Nephrol Dial Transplant. 1999;14(Suppl. 2):S50–60
Gastaldello K, Vereerstraeten A, Nzame-Nze T, Vanherweghem JL, Tielemans C. Resistance to erythropoietin in ironoverloaded haemodialysis patients can be overcome by ascorbic acid administration. Nephrol Dial Transplant. 1995;10(Suppl. 6):44–7
Tarng DC, Huang TP. A parallel, comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload. Nephrol Dial Transplant. 1998;13:2867–72
Tarng DC, Wei YH, Huang TP, Kuo BI, Yang WC. Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int. 1999;55:2477–86
Giancaspro V, Nuzziello M, Pallotta G, Sacchetti A, Petrarulo F. Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial. J Nephrol. 2000;13:444–9
Sezer S, Ozdemir FN, Yakupoglu U, Arat Z, Turan M, Haberal M. Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients. Artif Organs. 2002;26:366–70
Keven K, Kutlay S, Nergizoglu G, Ertrürk S. Randomized, crossover study of the effect of vitamin C on EPO response in hemodialysis patients. Am J Kidney Dis. 2003;41:1233–9
Deicher R, Ziai F, Habicht A, Bieglmayer C, Schillinger M, Hörl WH. Vitamin C level and response to erythropoietin in patients on chronic hemodialysis. Nephrol Dial Transplant. 2004 (In press)
Trovato GM, Ginardi V, Di Marco V, Dell ’Aira AE, Corsi M. Long term L-carnitine treatment of chronic anaemia of patients with end-stage renal failure. Curr Ther Res. 1982;31:1042–9
Fagher B, Cederblad G, Monti M, Olsson L, Rasmussen B, Thysell H. Carnitine and left ventricular function in haemodialysis patients. Scand J Clin Lab Invest. 1985;45: 193–8
Nilsson-Ehle P, Cederblad G, Fagher B, Monti M, Thysell H. Plasma lipoproteins, liver function and glucose metabolism in haemodialysis patients: lack of effect of L-carnitine supplementation. Scand J Clin Lab Invest. 1985;45:179–84
Fagher B, Cederblad G, Eriksson M et al. L-Carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function. Scand J Clin Lab Invest. 1985;45:169–78
Bellinghieri G, Savica V, Barbera CM et al. L-Carnitine and platelet aggregation in uremic patients subjected to hemodialysis. Nephron. 1990;55:28–30
Hurot J-M, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol. 2002;13: 708–14
Labonia WD. L-Carnitine effects on anemia in hemodialyzed patients treated with erythropoietin. Am J Kidney Dis. 1995;26:757–64
Patrikarea A, Stamatelow K, Ntaountaki I, Papadakis IT. The effect of combined L-carnitine and erythropoietin administration on the anaemia and on the lipid profile of patients on hemodialysis. Nephrol Dial Transplant. 1996;11:A262
Megri K, Trombert JC, Zannier A. Effet de la L-carnitine chez les patients en hemodialysis chronique traitée par érythropoietine recombinante. Nephrologie. 1998;19:171 (abstract).
Caruso U, Leone L, Cravotto E, Nava D. Effects of L-carnitine on anemia in aged hemodialysis patients treated with recombinant human erythropoietin: a pilot study. Dial Transplant. 1998;27:498–506
Sloan RS, Kastan B, Rice SI et al. Quality of life during and between hemodialysis treatments: role of L-carnitine supplementation. Am J Kidney Dis. 1998;32:265–72
Kletzmayr J, Mayer G, Legenstein H et al. Anemia and carnitine supplementation in hemodialyzed patients. Kidney Int. 1999;69(Suppl.):93–106
Yoshida A, Morozumi K, Suganuma T et al. Angiotensinconverting enzyme inhibitor and anemia in a patient undergoing hemodialysis. Nephron. 1991;59:334–5 (letter)
Ertürk S, Ates K, Duman N, Karatan O, Erbay B, Ertug E. Unresponsiveness to recombinant human erythropoietin in haemodialysis patients: possible implications of angiotensinconverting enzyme inhibitors. Nephrol Dial Transplant. 1996;11:396–7 (letter)
Akpolat T, Gumus T, Bedir A, Adam B. Acute effect of trandolapril on serum erythropoietin in uremic and hypertensive patients. J Nephrol. 1998;11:94–7
Schiffl H, Lang SM. Angiotensin-converting enzyme inhibitors but not angiotensin II AT 1 receptor antagonists affect erythropoiesis in patients with anemia of end-stage renal disease. Nephron. 1999;81:106–8 (letter)
Hirakata H, Onoyama K, Iseki K, Kumagai H, Fujimi S, Omae T. Worsening of anemia induced by long-term use of captopril in hemodialysis patients. Am J Nephrol. 1984; 4:355–60
Hirakata H, Onoyama K, Hori K, Fujishima M. Participation of the renin-angiotensin system in the captopril-induced worsening of anemia in chronic hemodialysis patients. Clin Nephrol. 1986;26:27–32
Walter J. Does captopril decrease the effect of human recombinant erythropoietin in haemodialysis patients? Nephrol Dial Transplant. 1993;8:1428 (letter)
Dhont AW, Vanholder RC, Ringoir SMG. Angiotensinconverting enzyme inhibitors and higher erythropoietin requirement in chronic haemodialysis patients. Nephrol Dial Transplant. 1995;10:2107–9
Matsumura M, Nomura H, Koni I, Mabuchi H. Angiotensin-converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Nephron. 1997; 77:164–8
Hess E, Sperschneider H, Stein G. Do ACE inhibitors influence the dose of human recombinant erythropoietin in dialysis patients? Nephrol Dial Transplant. 1996;11: 749–51
Ertürk S, Nergizoglu G, Ates K, Duman N, Erbay B, Karatan O, Ertug AE. The impact of withdrawing ACE inhibitors on erythropoietin responsiveness and left ventricular hypertrophy in haemodialysis patients. Nephrol Dial Transplant. 1999;14:1912–16
Albitar S, Genin R, Fen-Chong M, Serveaux M-O, Bourgenon B. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant. 1998;13:1206–10
Abu-Alfa AK, Cruz D, Perazella MA, Mahnensmith RL, Simon D, Bia MJ. ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients. Am J Kidney Dis. 2000;35:1076–82
Conlon PJ, Albers F, Butterly D, Schwab SJ. ACE inhibitors do not affect erythropoietin efficacy in haemodialysis patients. Nephrol Dial Transplant. 1994;9:1358 (letter)
Cruz DN, Perazella MA, Abu-Alfa AK, Mahnensmith RL. Angiotensin-converting enzyme inhibitor therapy in chronic hemodialysis patients: any evidence of erythropoietin resistance? Am J Kidney Dis. 1996;28:535–40.
Charytan C, Goldfarb-Rumyantzev A, Wang YF, Schwenk MH, Spinowitz BS. Effect of angiotensin-converting enzyme inhibitors on response to erythropoietin therapy in chronic dialysis patients. Am J Nephrol. 1998;18:498–503
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;38:510–17
Chew CG, Weise MD, Disney APS. The effect of angiotensin II receptor antagonist on the exogenous erythropoietin requirement of haemodialysis patients. Nephrol Dial Transplant. 1999;14:2047 (letter)
Schwarzbeck A, Wittenmeier KW, Hällfritzsch U. Anaemia in dialysis patients as a side-effect of sartanes. Lancet. 1998;352:286 (letter)
Naito M, Kawashima A, Akiba T, Takanashi M. Effects of an angiotensin II receptor antagonist and angiotensinconverting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients. Am J Nephrol. 2003; 23:287–93
Kato A, Takita T, Furuhashi M et al. No effect of losartan on response to erythropoietin therapy in patients undergoing hemodialysis. Nephron. 2000;86:538–9 (letter)
Odabas AR, Cetinkaya R, Selcuk Y et al. The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis. Panminerva Med. 2003;45:59–62
Macdougall IC. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin. Nephrol Dial Transplant. 1999;14:1836–41
Miles AM, Markell MS, Daskalakis P et al. Anemia following renal transplantation: erythropoietin response and iron deficiency. Clin Transplant. 1997;11:313–15
Vanrenterghem Y, Ponticelli C, Morales JM et al. Prevalence and management of anemia in renal transplant recipients: a European survey. Am J Transplant. 2003;3:835–45
Kewalramani R, Winkelmayer WC, Rutstein M et al. Anemia in renal transplant recipients: an emerging concern. American Transplant Congress. 2003
Mix TCH, Kazmi W, Khan S et al. Anemia: a continuing problem following kidney transplantation. Am J Transplant. 2003;3:1426–33
Gill JS, Abichandani R, Khan S, Kausz AT, Pereira BJG. Opportunities to improve the care of patients with kidney transplant failure. Kidney Int. 2002;61:2193–200
Qunibi WY, Barri Y, Devol E, Al-Furayh O, Sheth K, Taher S. Factors predictive of post-transplant erythrocytosis. Kidney Int. 1991;40:1153–9
Almond MK, Tailor D, Kelsey SM, Cunningham J. Treatment of erythropoietin resistance with cyclosporin. Lancet. 1994;343:916–17
Almond MK, Tailor D. Marsh FP, Raftery MJ, Cunningham J. Increased erythropoietin requirements in patients with failed renal transplants returning to a dialysis programme. Nephrol Dial Transplant. 1994;9:270–3
Page B, Zingraff J. Resistance to rHuEPO and kidney graft rejection. Nephrol Dial Transplant. 1994;9:1696
Sumrani NB, Daskalakis P, Miles AM et al. Erythrocytosis after renal transplantation. A prospective analysis. ASAIO J. 1993;39:51–5
Nankivell BJ, Allen RDM, O’Connell PJ, Chapman JP. Erythrocytosis after renal transplantation: risk factors and relationship with GFR. Clin Transplant. 1995;9:375–82
Besarab A, Caro J, Jarrell BE, Francos G, Erslev AJ. Dynamics of erythropoiesis following renal transplantation. Kidney Int. 1987;32:526–36
Sun CH, Ward HJ, Paul WL, Koyle MA, Yanagawa N, Lee DB. Serum erythropoietin levels after renal transplantation. N Engl J Med. 1989;321:151–7.
Chua M-S, Barry C, Chen X, Salvatierra O, Sarwal MM. Molecular profiling of anemia in acute renal allograft rejection using DANN microarrays. Am J Transplat. 2003; 3:17–22
European MMF Cooperative Study Group. Mycophenolate mofetil in renal transplantation: 3-years results from the placebo-controlled trial. Transplantation. 1999;68:391–6
DeClerck YA, Ettenger RB, Ortega JA, Pennisi AJ. Macrocytosis and pure RBC anemia caused by azathioprine. Am J Dis Child. 1980;134:377–9
Creemers GJ, van Boven WPL, Lowenberg B, van der Heul C. Azathioprine-associated pure red cell aplasia. J Intern Med. 1993;233:85–7
Gossmann J, Kachel HG, Schoeppe W, Scheuermann EH. Anemia in renal transplant recipients caused by concomitant therapy with azathioprine and angiotensin-converting enzyme inhibitors. Transplantation. 1993;56:585–9
Morii M, Ueno K, Ogawa A et al. Impairment of mycophenolate mofetil absorption by iron ion. Clin Pharmacol Ther. 2000;68:613–16
Lorenz M, Woltzt M, Weigel G et al. Ferrous sulfate does not affect steady-state mycophenolate mofetil pharmacokinetics in kidney transplant recipients. Am J Kidney Dis. 2004;43:1098–103
Rigatto C, Parfrey P. Strategies to improve outcomes after renal transplantation. N Engl J Med. 2002;346:2089–92; author reply, 20–92
Rigatto C, Parfrey P, Foley R, Negrijn C, Tribula C, Jeffery J. Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. J Am Soc Nephrol. 2002;13:1084–90
Bostom AD, Brown RS, Chavers BM et al. Prevention of post-transplant cardiovascular disease — report and recommendations of an ad hoc group. Am J Transplant. 2002; 2:491–500
Rigatto C, Foley R, Jeffery J, Negrijn C, Tribula C, Parfrey P. Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia. J Am Soc Nephrol. 2003;14: 462–8
Casadevall N, Nataf J, Viron B et al. Pure red-cell aplasia and anti-erythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med. 2002;346:469–75
Gershon SK, Luksenburg H, Cote TR, Braun MM. Pure red-cell aplasia and recombinant erythropoietin. N Engl J Med. 2002;346:1584–5 (letter)
Pollock, C, Rossert J, Schellekens H. Pure red cell aplasia: highlights from the 2003 World Congress of Nephrology. Nexus Communications, 2003:4–10
Eckardt KU, Casadevall N. Pure red-cell aplasia due to anti-erythropoietin antibodies. Nephrol Dial Transplant. 2003;18:865–9
Weber G, Gross J, Kromminga A, Loew HH, Eckardt KU. Allergic skin and systemic reactions in a patient with pure red cell aplasia epoetins. J Am Soc Nephrol. 2002;13: 2381–3
Chng WJ, Tan LK, Liu TC. Cyclosporine treatment for patients with CRF who developed pure red cell aplasia following EPO therapy. Am J Kidney Dis. 2003;41: 692–5
Panchapakesan U, Austin SK, Shafransky A, Lawrence JA, Savdie E. Recovery of pure red-cell aplasia secondary to antierythropoietin antibodies after cessation of recombinant human erythropoietin. Intern Med J. 2003;33:468–71
Locatelli F, Aljama P, Barany P et al. Erythropoiesis stimulating agents and antibody-mediated pure red cell aplasia: where are we now and where do we go from here? Nephrol Dial Transplant. 2004;19:288–93.
Pure Red Cell Aplasia Global Scientific Advisory Board (GSAB). Erythropoietin-induced, antibody-mediated pure red cell aplasia. Eur J Clin Invest. 2004 (In press).
Swanson SJ, Ferbas J, Mayeux P, Casadevall N. Evaluation of methods to detect and characterize antibodies against recombinant human erythropoietin. Nephron. 2004 (In press).
Bunn HF. Drug-induced autoimmune red-cell aplasia. N Engl J Med. 2002;346:522–3.
Skibeli V, Nissen-Lie G, Torjesen P. Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin. Blood. 2001;98:3626–34.
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Hörl, W.H. (2004). Management of anemia in patients with chronic kidney disease. In: Hörl, W.H., Koch, K.M., Lindsay, R.M., Ronco, C., Winchester, J.F. (eds) Replacement of Renal Function by Dialysis. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-2275-3_39
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