Erythropoetin – ein aktueller Überblick

Zusammenfassung

Der Mangel an Erythropoetin (EPO) ist die entscheidende Ursache der renalen Anämie und kann durch Epoetin-Substitution in fast allen Fällen erfolgreich behandelt werden. Seit der gentechnologischen Herstellung des rekombinanten Epoetins ist das Hormon gut verfügbar und durch Biosimilars auch wirtschaftlich einsetzbar. Die Behandlung mit den verfügbaren Erythropoese stimulierenden Agenzien (ESAs) kann durch umfassende Erkenntnisse aus klinischen Studien optimiert und sicher durchgeführt werden. Unerwünschte schwere Nebenwirkungen der EPO-Therapie sind insgesamt selten, stellen den Behandler dennoch im Einzelfall vor eine Herausforderung. Insbesondere bei Anheben der Hb-Werte (Hb: Hämoglobin) auf>13 g/dl ist mit dem Auftreten von Schlaganfällen und venösen Thromboembolien zu rechnen. Dieser Artikel greift die Inhalte der aktualisierten, noch in 2025 zu publizierenden KDIGO-Leitlinie zur renalen Anämie auf, die ein individuelles diagnostisches und therapeutisches Vorgehen beim Einsatz von EPO betont.

Abstract

Erythropoietin (EPO) deficiency is the primary cause of renal anemia and can be effectively treated with EPO substitution in most cases. Since the advent of recombinant EPO production, this hormone has become widely accessible, and biosimilars now provide cost-effective treatment alternatives. Based on the evidence from clinical studies, the use of erythropoiesis-stimulating agents (ESAs) can be carried out with improved safety and efficacy. Severe adverse effects are rare but may present challenges, particularly when hemoglobin levels rise above 13 g/dL, which increases the risk of stroke and venous thromboembolism. This article reviews the public draft of updated KDIGO 2025 guideline on renal anemia, with a focus on individualized diagnostic and therapeutic approaches for EPO therapy.

Schlüsselwörter

Renale Anämie - Erythropoetin-stimulierende Substanzen - ESA - Eryhthropoese - EPO - Chronische Nierenkrankheit

Keywords

Renal anemia - Erythropoiesis-Stimulating Agents - ESA - Erythropoiesis - Erythropoietin (EPO) - Chronic kidney disease (CKD)

Publikationsverlauf

Artikel online veröffentlicht:
25. November 2025

• Literatur

• 1 Elliott S, Pham E, Macdougall IC. Erythropoietins: a common mechanism of action. Exp Hematol 2008; 36: 1573-1584
• 2 Eknoyan G, Lameire N, Winkelmayer W. et al. Public-Review-Draft KDIGO 2025 Clinical Practice Guideline For Anemia In Chronic Kidney Disease (CKD). 2024 Im Internet https://kdigo.org/wp-content/uploads/2024/11/KDIGO-2025-Anemia-in-CKD-Guideline_Public-Review-Draft_Nov42024.pdf Stand: 16.02.2025
• 3 Singh AK, Carroll K, Perkovic V. et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med 2021; 385: 2325-2335
• 4 Eckardt KU, Agarwal R, Aswad A. et al. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med 2021; 384: 1601-1612
• 5 Akizawa T, Iwasaki M, Otsuka T. et al. Phase 3 Study of Roxadustat to Treat Anemia in Non-Dialysis-Dependant CKD. Kidney Int Rep 2021; 6: 1810-1828
• 6 Ha JT, Hiremath S, Jun M. et al. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease. NEJM Evid 2024; 3: EVIDoa2300189
• 7 Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 2013; 27: 41-53
• 8 Keller F, Schroppel B, Ludwig U. Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction. World J Nephrol 2015; 4: 330-344
• 9 Broxmeyer HE. Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration. J Exp Med 2013; 210: 205-208
• 10 McFarlane SI, Chen SC, Whaley-Connell AT. et al. Prevalence and associations of anemia of CKD: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis 2008; 51: S46-S55
• 11 Rosenberger C. Renale Anämie. In: Akademie Niere, Hrsg. Lehrbuch für Nieren- und Hochdruckkrankheiten. Lengerich: Pabst Science; 2024: 327-358
• 12 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: 578-583
• 13 Wright DG, Wright EC, Narva AS. et al. Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States. Clin J Am Soc Nephrol 2015; 10: 1822-1830
• 14 Hahn D, Esezobor CI, Elserafy N. et al. Short-acting erythropoiesis-stimulating agents for anaemia in predialysis patients. Cochrane Database Syst Rev 2017; 1: CD011690
• 15 Keller F, Ludwig U, Czock D. Pharmacokinetic and pharmacodynamic considerations on the erythropoietin effect and adverse events of darbepoetin. Expert Opin Drug Metab Toxicol 2015; 11: 139-147
• 16 Epoetin alfa. Erypo FS. Fachinformation. Janssen. Stand Juni 2021. In: Rote-Liste. Im Internet https://www.fachinfo.de Stand: 16.02.2025
• 17 Rosenberger C. Renale Anämie. In: Akademie Niere, Hrsg. Lehrbuch für Nieren- und Hochdruckkrankheiten. Lengerich: Pabst Science; 2022: 317-346
• 18 Pfeffer MA, Burdmann EA, Chen CY. et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361: 2019-2032
• 19 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: 584-590
• 20 Rene E, Lazrak HH, Laurin LP. et al. Association of erythropoiesis-stimulating agents and the incidence risk of cancer diagnosis among chronic dialysis patients: a nested case-control study. Nephrol Dial Transplant 2017; 32: 1047-1052
• 21 Bohlius J, Schmidlin K, Brillant C. et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet 2009; 373: 1532-1542
• 22 Henke M, Laszig R, Rube C. et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003; 362: 1255-1260
• 23 Ku E, Del Vecchio L, Eckardt KU. et al. Novel anemia therapies in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2023; 104: 655-680
• 24 No authors listed IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: update 2000. Am J Kidney Dis 2001; 37: S182-S238
• 25 Panichi V, Rosati A, Bigazzi R. et al. Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study. Nephrol Dial Transplant 2011; 26: 2641-2648
• 26 Eknoyan G, Lameire N, Winkelmayer W. et al. Public-Review-Draft KDIGO 2025 Clinical Practice Guideline For Anemia In Chronic Kidney Disease (CKD). 2024: 288-335 Im Internet https://kdigo.org/wp-content/uploads/2024/11/KDIGO-2025-Anemia-in-CKD-Guideline_Public-Review-Draft_Nov42024.pdf Stand: 16.02.2025
• 27 Mikhail A, Brown C, Williams JA. et al. Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease. BMC Nephrol 2017; 18: 345
• 28 Casadevall N, Eckardt KU, Rossert J. Epoetin-induced autoimmune pure red cell aplasia. J Am Soc Nephrol 2005; 16: S67-S69
• 29 Haufe C. Renale Anämie. Nephrologe 2019; 14: 305-317
• 30 Ma X, Pai P, Zhu W. et al. Positive response of a hemodialysis patient with pure red cell aplasia on recombinant human erythropoietin therapy to cyclosporine and Roxadustat. CEN Case Rep 2024; 13: 445-449