Innovations in the treatment of anemia in chronic kidney failure

Öz

Chronic kidney disease (CKD) is a chronic inflammatory process. Inflammation, uremic toxins, deficiency of erythropoietin production, iron deficiency, shortening of erythrocyte lifespan, gastrointestinal losses, etc. lead to anemia in CKD. The prevalence of anemia increases as the CKD stage increases. Hepcidin is an important molecule for the use of iron in anemia. Hypoxia-induced factors (HIF) maintain the continuity of erythropoiesis. This molecule is inactivated by prolyl hydroxylase (PH). HIF-PH inhibitors have come into use in the treatment of anemia due to CKD. This review describes anemia in CKD and the use of HIF PH inhibitors.

Anahtar Kelimeler

• Chronic kidney disease
• anemia
• hepcidin
• HIF-PH inhibitors.

Destekleyen Kurum

None

Kaynakça

1. Iseki K, Kohagura K. Anemia as a risk factor for chronic kidney disease. Kidney Int Suppl 2007;(107):S4-9.
2. Stauffer ME, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One 2014;9(1):e84943.
3. Astor BC, Coresh J, Heiss G, Pettitt D, Sarnak MJ. Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2006;151(2):492-500.
4. Weiner DE, Tighiouart H, Vlagopoulos PT, Griffith JL, Salem DN, Levey AS, Sarnak MJ. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 2005;16(6):1803-10.
5. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Lambers Heerspink HJ, Mann JF, Matsushita K, Wen CP. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 2013;382(9889):339-52.
6. Eckardt KU. Anaemia in end-stage renal disease: pathophysiological considerations. Nephrol Dial Transplant 2001;16 Suppl 7:2-8.
7. Mathias SD, Blum SI, Sikirica V, Johansen KL, Colwell HH, Tony Okoro T. Symptoms and impacts in anemia of chronic kidney disease. J Patient Rep Outcomes 2020;4(1):64.
8. Lasocki S, Longrois D, Montravers P, Beaumont C. Hepcidin and anemia of the critically ill patient: bench to bedside. Anesthesiology 2011;114(3):688-94.

9. Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica 2020;105(2):260-72.
10. Koury MJ, Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol 2015;11(7):394-410.
11. Prabhakar NR, Semenza GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev 2012;92(3):967-1003.
12. Locatelli F, Fishbane S, Block GA, Macdougall IC. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am J Nephrol 2017;45(3):187-199.
13. Schödel J, Ratcliffe PJ. Mechanisms of hypoxia signalling: new implications for nephrology. Nat Rev Nephrol 2019;15(10):641-59.
14. Mikhail A, Brown C, Williams JA, Mathrani V, Shrivastava R, Evans J, Isaac H, Bhandari S. Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease. BMC Nephrol 2017;18(1):345.
15. Auerbach M, Macdougall IC. Oral Iron Therapy: After Three Centuries, It Is Time for a Change. Am J Kidney Dis 2016;68(5):665-6.
16. Drüeke TB, Massy ZA. Oral or intravenous iron for anemia correction in chronic kidney disease? Kidney Int 2015;88(4):673-5.
17. Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012;23(10):1631-4.
18. Sahu S, Hemlata, Verma A. Adverse events related to blood transfusion. Indian J Anaesth 2014;58(5):543-51.
19. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA. 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(9):584-90.
20. Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A; CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355(20):2071-84.
21. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JMet al.; TREAT Investigators. N Engl J Med 2009;361(21):2019-32.
22. Locatelli F, Fishbane S, Block GA, Macdougall IC. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am J Nephrol 2017;45(3):187-99.
23. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004;5(5):343-54.
24. Shutov E, Sułowicz W, Esposito C, Tataradze A, Andric B, Reusch M, Valluri U, Dimkovic N. Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS). Nephrol Dial Transplant. 2021;36(9):1629-39.
25. Fishbane S, El-Shahawy MA, Pecoits-Filho R, Van BP, Houser MT, Frison L, Little DJ et al. Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study. J Am Soc Nephrol 2021;32(3):737-55.
26. Coyne DW, Roger SD, Shin SK, Kim SG, Cadena AA, Moustafa MA, Chan TM et al. Roxadustat for CKD-related Anemia in Non-dialysis Patients. Kidney Int Rep 2020;6(3):624-35.
27. Barratt J, Andric B, Tataradze A, Schömig M, Reusch M, Valluri U, Mariat C. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES). Nephrol Dial Transplant 2021;36(9):1616-28.
28. Charytan C, Manllo-Karim R, Martin ER, Steer D, Bernardo M, Dua SL, Moustafa MA et al. A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study. Kidney Int Rep 2021;6(7):1829-39.
29. Barratt J, Sulowicz W, Schömig M, Esposito C, Reusch M, Young J, Csiky B. Efficacy and Cardiovascular Safety of Roxadustat in Dialysis-Dependent Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther 2021;38(10):5345-60.