Therapie der renalen Anämie

ZUSAMMENFASSUNG

Die Einführung von Präparaten mit Erythropoietin (EPO)/Erythropoese stimulierenden Agenzien (ESA) zur Behandlung der renalen Anämie Ende der 1980er-Jahre ermöglichte eine Einsparung von Blutkonserven und eine Verbesserung der Lebensqualität von chronisch nierenkranken und v. a. dialysepflichtigen Patienten. Nach den negativen Ergebnissen der großen EPO/ESA-Endpunktstudien Mitte der 1990er-Jahre, erschien mit PIVOTAL 2019 eine randomisierte Studie zur intravenösen Eisentherapie, die eine prognostische Überlegenheit einer Hochdosiseisentherapie gegenüber einer restriktiveren Eisenapplikation zeigte. Mit den HIF-Stabilisatoren (HIF: Hypoxie induzierbarer Faktor) wird jetzt eine weitere – orale – Behandlungsoption der renalen Anämie verfügbar. Phase-II- und Phase-III-Studien zeigten eine Nichtunterlegenheit im Hinblick auf den Hämoglobinanstieg gegenüber einer Behandlung mit EPO/ESA-Präparaten. Da HIF-Stabilisatoren in die Transkription von unterschiedlichsten Genen eingreifen, müssen Sicherheitsstudien weitere wichtige Erkenntnisse liefern.

• Literatur

• 1 Hsu CY, McCulloch CE, Curhan 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: 504-510
• 2 El-Achkar TM, Ohmit SE, McCullough PA. et al Higher prevalence of anemia with diabetes mellitus in moderate kidney insufficiency: The Kidney Early Evaluation Program. Kidney Int 2005; 67: 1483-1488
• 3 Moreno F, Lopez Gomez JM, Sanz-Guajardo D. et al Quality of life in dialysis patients. A Spanish multicentre study. Nephrol Dial Transplant 1996; 11: 125-129
• 4 Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999; 10: 610-619
• 5 Levin A, Singer J, Thompson CR. et al Prevalent left ventricular hypertrophy in the predialysis population: Identifying opportunities for intervention. Am J Kidney Dis 1996; 27: 347-354
• 6 Vlagopoulos PT, Tighiouart H, Weiner DE. et al Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: The impact of chronic kidney disease. J Am Soc Nephrol 2005; 16: 3403-3410
• 7 Keane WF, Brenner BM, De Zeeuw D. et al The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: The RENAAL study. Kidney Int 2003; 63: 1499-1507
• 8 MacDougall IC, Obrador GT. How important is transfusion avoidance in 2013?. Nephrol Dial Transplant 2013; 28: 1092-1099
• 9 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
• 10 Singh AK, Szczech L, Tang KL. et al Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085-2098
• 11 Drüeke TB, Locatelli F, Clyne N. et al Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071-2084
• 12 Pfeffer MA, Burdmann EA, Chen C-Y. et al A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. N Engl J Med 2009; 361: 2019-2032
• 13 Coyne DW. From anemia trials to clinical practice: Understanding the risks and benefits when setting goals for therapy. Semin Dial 2008; 21: 212-216
• 14 KDIGO KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012: 2
• 15 Chertow GM, Liu J, Monda KL. et al Epoetin alfa and outcomes in dialysis amid regulatory and payment reform. J Am Soc Nephrol 2016; 27: 3129-3138
• 16 Besarab A, Flaharty KK, Erslev AJ. et al Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration. J Am Soc Nephrol 1992; 02: 1405-1416
• 17 Andrews NC. Closing the Iron Gate. N Engl J Med 2012; 366: 376-377
• 18 Macdougall IC, Bock AH, Carrera F. et al FIND-CKD: A randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014; 29: 2075-2084
• 19 Winkelmayer WC, Mitani AA, Goldstein BA. et al Trends in anemia care in older patients approaching end-stage renal disease in the United States (1995–2010). JAMA Intern Med 2014; 174: 699-707
• 20 Macdougall IC, White C, Anker SD. et al Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med 2019; 380: 447-458
• 21 Bailie GR, Larkina M, Goodkin DA. et al Data from The dialysis outcomes and practice patterns study validate an association between high intravenous iron doses and mortality. Kidney Int 2015; 87: 162-168
• 22 Bhandari S, Kalra PA, Berkowitz M. et al Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: The FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant 2021; 36: 111-120
• 23 Zoller H, Schaefer B, Glodny B. Iron-induced hypophosphatemia. Curr Opin Nephrol Hypertens 2017; 26: 266-275
• 24 Wolf M, Rubin J, Achebe M. et al Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA 2020; 323: 432-443
• 25 Emrich IE, Lizzi F, Siegel JD. et al Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose—the randomized controlled HOMe aFers study. BMC Med 2020; 18: 178
• 26 Babitt JL, Eisenga MF, Haase VH. et al Controversies in Optimal Anemia Management: Conclusions from a Kidney Disease Improving Global Outcomes (KDIGO) Conference. Kidney Int 2021; 99: 1280-1295
• 27 Emrich IE, Böhm M, Heine GH. Anemia and iron deficiency – Treatment options in chronic kidney disease and in chronic heart failure. Dtsch Med Wochenschr 2020; 145: 1775-1780
• 28 Kurata Y, Tanaka T, Nangaku M. Hypoxia-inducible factor prolyl hydroxylase inhibitor in the treatment of anemia in chronic kidney disease. Curr Opin Nephrol Hypertens 2020; 29: 414-422
• 29 Chen N, Hao C, Liu BC. et al Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med 2019; 381: 1011-1022
• 30 Chen N, Hao C, Peng X. et al Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med 2019; 381: 1001-1010