Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Lamerato L, James G, van Haalen H, Hedman K, Sloan JA, Tang A, et al. Epidemiology and outcomes in patients with anemia of CKD not on dialysis from a large US healthcare system database: a retrospective observational study. BMC Nephrol. 2022;23:166.

CAS  PubMed  PubMed Central  Google Scholar 

Locatelli F, Pisoni RL, Combe C, Bommer J, Andreucci VE, Piera L, 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(1):121–32.

PubMed  Google Scholar 

Available at: https://www.who.int/health-topics/anaemia#tab=tab_1 Last viewed on the 17th of June, 2022

Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med. 1987;316(2):73–8.

CAS  PubMed  Google Scholar 

Winearls CG, Pippard MJ, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet. 1986;ii:1175–7.

Google Scholar 

Locatelli F, Del Vecchio L, De Nicola L, Minutolo R. Are all erythropoiesis-stimulating agents created equal? Nephrol Dial Transplant. 2021;36(8):1369–77.

CAS  PubMed  Google Scholar 

Praditpornsilpa K, Tiranathanagul K, Kupatawintu P, Jootar S, Intragumtornchai T, Tungsanga K, et al. Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies. Kidney Int. 2011;80(1):88–92.

CAS  PubMed  Google Scholar 

Lewis EF, Pfeffer MA, Feng A, Uno H, McMurray JJV, Toto R, et al. TREAT Investigators. Darbepoetin alfa impact on health status in diabetes patients with kidney disease: a randomized trial. Clin J Am Soc Nephrol. 2011;6:845–55.

CAS  PubMed  PubMed Central  Google Scholar 

McFarlane PA, Pisoni RL, Eichleay MA, Wald R, Port FK, Mendelssohn D. International trends in erythropoietin use and hemoglobin levels in hemodialysis patients. Kidney Int. 2010;78:215–23.

CAS  PubMed  Google Scholar 

Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, de Zeeuw D, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363(12):1146–55.

CAS  PubMed  Google Scholar 

Cizman B, Smith HT, Camejo RR, Casillas L, Dhillon H, Mu F, et al. Clinical and economic outcomes of erythropoiesis-stimulating agent hyporesponsiveness in the post-bundling era. Kidney Med. 2020;2(5):589–99.

PubMed  PubMed Central  Google Scholar 

Malyszko J, Malyszko JS, Mysliwiec M. Hyporesponsiveness to erythropoietin therapy in hemodialyzed patients: potential role of prohepcidin, hepcidin, and inflammation. Ren Fail. 2009;31(7):544–8.

CAS  PubMed  Google Scholar 

Yusipov I, Kondakova E, Kalyakulina A, Krivonosov M, Lobanova N, Bacalini MG, et al. Accelerated epigenetic aging and inflammatory/immunological profile (ipAGE) in patients with chronic kidney disease. Geroscience. 2022;44(2):817–34.

CAS  PubMed  PubMed Central  Google Scholar 

Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, 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(9):584–90.

CAS  PubMed  Google Scholar 

Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071-84.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–98.

Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, et al. TREAT Investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361(21):2019–32.

PubMed  Google Scholar 

Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2:279–335.

Macdougall IC, White C, Anker SD, Bhandari S, Farrington K, Kalra PA, et al. PIVOTAL Investigators and Committees. Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med. 2019;380(5):447–58.

CAS  PubMed  Google Scholar 

De Nicola L, Locatelli F, Conte G, Minutolo R. Responsiveness to erythropoiesis-stimulating agents in chronic kidney disease: does geography matter? Drugs. 2014;74(2):159–68.

PubMed  Google Scholar 

Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol. 1992;12(12):5447–54.

CAS  PubMed  PubMed Central  Google Scholar 

Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995;92(12):5510–4.

CAS  PubMed  PubMed Central  Google Scholar 

Webb JD, Coleman ML, Pugh CW. Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell Mol Life Sci. 2009;66(22):3539–54.

CAS  PubMed  Google Scholar 

Maxwell PH, Eckardt KU. HIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyond. Nat Rev Nephrol. 2016;12(3):157–68.

CAS  PubMed  Google Scholar 

Chan MC, Ilott NE, Schödel J, Sims D, Tumber A, Lippl K, et al. Tuning the transcriptional response to hypoxia by inhibiting hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. J Biol Chem. 2016;291(39):20661–73.

CAS  PubMed  PubMed Central  Google Scholar 

Mole DR, Blancher C, Copley RR, Pollard PJ, Gleadle JM, Ragoussis J, et al. Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem. 2009;284(25):16767–75.

CAS  PubMed  PubMed Central  Google Scholar 

Brookhart MA, Schneeweiss S, Avorn J, Bradbury BD, Rothman KJ, Fischer M, et al. The effect of altitude on dosing and response to erythropoietin in ESRD. J Am Soc Nephrol. 2008;19(7):1389–95.

CAS  PubMed  PubMed Central  Google Scholar 

Sibbel S, Maroni BJ, Brunelli SM. The effect of altitude on erythropoiesis-stimulating agent dose, hemoglobin level, and mortality in hemodialysis patients. J Nephrol. 2017;30(6):821–9.

CAS  PubMed  Google Scholar 

Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, Günzler V, et al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010;21(12):2151–6.

CAS  PubMed  PubMed Central  Google Scholar 

Yeh TL, Leissing TM, Abboud MI, Thinnes CC, Atasoylu O, Holt-Martyn JP, et al. Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Chem Sci. 2017;8(11):7651–68.

CAS  PubMed  PubMed Central  Google Scholar 

Sulser P, Pickel C, Günter J, Leissing TM, Crean D, Schofield CJ, et al. HIF hydroxylase inhibitors decrease cellular oxygen consumption depending on their selectivity. FASEB J. 2020;34(2):2344–58.

CAS  PubMed  Google Scholar 

Coyne DW, Singh AK, Lopes RD, Bailey CK, DiMino TL, Huang C, et al. Three times weekly dosing of daprodustat versus conventional epoetin for treatment of anemia in hemodialysis patients: ASCEND-TD: a phase 3 randomized, double-blind, noninferiority trial. Clin J Am Soc Nephrol. 2022;17:1325–36 (Epub ahead of print).

Coyne DW, Roger SD, Shin SK, Kim SG, Cadena AA, Moustafa MA, et al. Roxadustat for CKD-related anemia in non-dialysis patients. Kidney Int Rep. 2020;6(3):624–35.

PubMed  PubMed Central  Google Scholar 

Shutov E, Sułowicz W, Esposito C, Tataradze A, Andric B, Reusch M, et al. 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.

Fishbane S, El-Shahawy MA, Pecoits-Filho R, Van BP, Houser MT, Frison L, 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.

Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med. 2019;381(11):1001-10.

Barratt J, Andric B, Tataradze A, Schömig M, Reusch M, Valluri U, et al. 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.

Akizawa T, Iwasaki M, Otsuka T, Yamaguchi Y, Reusch M. Phase 3 Study of roxadustat to treat anemia in non-dialysis-dependant CKD. Kidney Int Rep. 2021;6(7):1810-28.

Yamamoto H, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Akizawa T. Molidustat for renal anemia in nondialysis patients previously treated with erythropoiesis-stimulating agents: a randomized, open-label, phase 3 study. Am J Nephrol. 2021;52(10-11):884-93.

Yamamoto H, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Akizawa T. Efficacy and safety of molidustat for anemia in ESA-naive nondialysis patients: a randomized, phase 3 trial. Am J Nephrol. 2021;52(10-11):871-83.

Singh AK, Carroll K, McMurray JJV, Solomon S, Jha V, Johansen KL, et al. Daprodustat for the treatment of anemia in patients not undergoing dialysis. N Engl J Med. 2021;385(25):2313-24.

Akizawa T, Nangaku M, Yamaguchi T, Koretomo R, Maeda K, Miyazawa Y, et al. A phase 3 study of enarodustat in anemic patients with CKD not requiring dialysis: The SYMPHONY ND Study. Kidney Int Rep. 2021;6(7):1840-49.

Nangaku M, Kondo K, Kokado Y, Ueta K, Kaneko G, Tandai T, et al. Phase 3 randomized study comparing vadadustat with darbepoetin alfa for anemia in Japanese patients with nondialysis-dependent CKD. J Am Soc Nephrol. 2021;32(7):1779-90.

Chertow GM, Pergola PE, Farag YMK, Agarwal R, Arnold S, Bako G, et al. Vadadustat in patients with anemia and non-dialysis-dependent CKD. N Engl J Med. 2021;384(17):1589-1600.

Agrawal D, Varade D, Shah H, Nazar A, Krishnan J, Shukla V, et al. Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND). Am J Nephrol. 2022;53(5):352-60.

Provenzano R, Shutov E, Eremeeva L, Korneyeva S, Poole L, Saha G, et al. Roxadustat for anemia in patients with end-stage renal disease incident to dialysis. Nephrol Dial Transplant. 2021;36(9):1717-30.

Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, et al. Safety and efficacy of vadadustat for anemia in patients undergoing dialysis. N Engl J Med. 2021;384(17):1601-12.

Charytan C, Manllo-Karim R, Martin ER, Steer S, Bernardo M, Dua SL, et al. A randomized trial of roxadustat in anemia of kidney failure: SIERRAS Study. Kidney Int Rep. 2021;6(7):1829-39.

Csiky B, Schömig M, Esposito C, Barratt J, Reusch M, Valluri U, et al. Roxadustat for the maintenance treatment of anemia in patients with end-stage kidney disease on stable dialysis: a European phase 3, randomized, open-label, active-controlled study (PYRENEES). Adv Ther. 2021;38(10):5361-80.

Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan. J Am Soc Nephrol. 2020;31(7):1628-39.

Chen N, Hao C, Liu BC, Lin H, Wang C, Xing C, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med. 2019;381(11):1011-22.

Akizawa T, Yamada T, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, et al. Molidustat for Japanese patients with renal anemia receiving dialysis. Kidney Int Rep. 2021;6(10):2604-16.

Akizawa T, Nangaku M, Yamaguchi T, Koretomo R, Maeda K, Miyazawa Y, et al. A Phase 3 study of enarodustat (JTZ-951) in Japanese hemodialysis patients for treatment of anemia in chronic kidney disease: SYMPHONY HD study. Kidney Dis (Basel). 2021;7(6):494-502.

Singh AK, Carroll K, Perkovic V, Solomon S, Jha V, Johansen KL, et al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N Engl J Med. 2021;385(25):2325-35.

Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, Onoue T, et al. Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia: a randomized, double-blind, phase 3 trial. Clin J Am Soc Nephrol. 2020;15(8):1155-1165.

Nangaku M, Kondo K, Ueta K, Kokado Y, Kaneko G, Matsuda H, et al. Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study. Nephrol Dial Transplant. 2021;36(9):1731-41.

Singh AK, Cizman B, Carroll K, McMurray JJV, Perkovic V, Jha V, et al. Efficacy and safety of daprodustat for treatment of anemia of chronic kidney disease in incident dialysis patients: a randomized clinical trial. JAMA Intern Med. 2022;182(6):592-602.

Fishbane S, Pollock CA, El-Shahawy M, Escudero ET, Rastogi A, Van BP, et al. Roxadustat versus epoetin alfa for treating anemia in patients with chronic kidney disease on dialysis: results from the randomized phase 3 ROCKIES study. J Am Soc Nephrol. 2022;33(4):850-66.

Gang S, Khetan P, Varade D, Chinta VR, Mavani S, Gupta U, et al. Desidustat in anemia due to dialysis-dependent chronic kidney disease: a phase 3 study (DREAM-D). Am J Nephrol. 2022;53(5):343–51.

CAS  PubMed  Google Scholar 

Chen H, Cheng Q, Wang J, Zhao X, Zhu S. Long-term efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in anaemia of chronic kidney disease: a meta-analysis including 13,146 patients. J Clin Pharm Ther. 2021;46(4):999–1009.

CAS  PubMed  Google Scholar 

Akizawa T, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Yamamoto H. Molidustat for the treatment of anemia in Japanese patients undergoing peritoneal dialysis: a single-arm, open-label, phase 3 study. Ther Apher Dial. 2022;6(2):368–77.

Google Scholar 

Hou YP, Mao XY, Wang C, Xu ZH, Bu ZH, et al. Roxadustat treatment for anemia in peritoneal dialysis patients: a randomized controlled trial. J Formos Med Assoc. 2022;121(2):529–38.

CAS  PubMed  Google Scholar 

Choukroun G, Kamar N, Dussol B, Etienne I, Cassuto-Viguier E, Toupance O, et al. Correction of postkidney transplant anemia reduces progression of allograft nephropathy. J Am Soc Nephrol. 2012;23(2):360–8.

CAS  PubMed  PubMed Central  Google Scholar 

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