Chapter 33
Treatment of Anemia in Chronic Kidney Disease
Patrick S. Parfrey,
Patrick S. Parfrey
Faculty of Medicine, Memorial University, St. John's, NL, Canada
Search for more papers by this authorPatrick S. Parfrey,
Patrick S. Parfrey
Faculty of Medicine, Memorial University, St. John's, NL, Canada
Search for more papers by this authorBook Editor(s):Jonathan C. Craig MBChB, DipCH, MMed(Clin Epi), PhD, FAHMS,
Donald A. Molony MD,
Giovanni F.M. Strippoli MD, PhD, MPH, MM (Epi),
Jonathan C. Craig MBChB, DipCH, MMed(Clin Epi), PhD, FAHMS
Matthew Flinders Distinguished Professor Vice President and Executive Dean
College of Medicine and Public Health, Flinders University, Adelaide, Australia
Search for more papers by this authorDonald A. Molony MD
Professor of Medicine Distinguished Teaching Professor of the University of Texas System
Division of Renal Diseases and Hypertension AND Center for Clinical Research and Evidence-based Medicine, McGovern Medical School University of Texas, Houston, TX, USA
Search for more papers by this authorGiovanni F.M. Strippoli MD, PhD, MPH, MM (Epi)
Professor of Nephrology Adjunct Professor of Epidemiology
Department of Emergency and Organ Transplantation – University of Bari, Bari, Italy
School of Public Health, University of Sydney, Sydney, NSW, Australia
Search for more papers by this authorFirst published: 18 November 2022
Summary
The prevalence of anemia increases as chronic kidney disease (CKD) progresses by stage. Anemia is caused by erythyropoietin deficiency, disordered iron metabolism, blood loss, infection, inflammation, and other less frequentcauses. The choice of interventions to treat or prevent anemia in CKD should be influenced by the results of randomized controlled trials. Recombinant human erythropoietins have been used to treat anemia for up to three decades. Hypoxia inducible factor is the major transcription factor for the erythropoietin gene. Liver production can respond to prolyl hydroxylase inhibition by producing more endogenous erythropoietin. Current management of anemia in CKD usually combines use of erythropoiesis-stimulating agents (ESAs) and iron repletion, and is driven by the need to avoid both severe anemia and the risk of blood transfusions, and normal hemoglobin levels, which were associated with increased cardiovascular risk in ESA trials.
References
- Skali , H. , Lin , J. , Pfeffer , M.A. et al. ( 2013 ). Hemoglobin stability in patients with anemia, CKD and type 2 diabetes: an analysis of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) Placebo arm . Am. J. Kidney Dis. 61 : 238 – 246 .
- McCausland , F.R. , Claggett , B. , Pfeffer , M.A. et al. ( 2017 ). Change in hemoglobin trajectary and darbepoetin dose approaching end-stage renal disease: data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy . Am. J. Nephrol. 46 : 488 – 497 .
- Canadian Erythropoietin Study Group ( 1990 ). Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving hemodialysis . BMJ 200 : 573 – 578 .
- Wheeler , D.C. , London , G.M. , Parfrey , P.S. et al. ( 2014 ). Effects of cinacalcet on atherosclerotic and non-atherosclerotic cardiovascular events in patients receiving hemodialysis: The EValuation of Cinacalcet Therapy to Lower Cardiovascular Events trial . J. Am. Heart Assoc. 3 ( 6 ): e001363 . https://doi.org/10.1161/JAHA.114.001363 .
- Vlagopoulos , P.T. , Tighiouart , H. , Weiner , D.E. et al. ( 2005 ). Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease . J. Am. Soc. Nephrol. 16 : 3403 – 3410 .
- Weiner , D.E. , Tighiouart , H. , Vlagopoulos , P.T. et al. ( 2005 ). Effects of anemia and left ventricularhypertrophy on cardiovascular disease in patients with chronic kidney disease . J. Am. Soc. Nephrol. 16 : 1803 – 1810 .
- Chang , J.M. , Chen , S.C. , Huang , J.C. et al. ( 2014 ). Anemia and left ventricular hypertrophy wit renal function decline and cardiovascular events in chronic kidney disease . Am J Med Sci 347 : 183 – 189 .
- Besarab , A. , Bolton , W.K. , Browne , J.K. et al. ( 1998 ). 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. 339 : 584 – 590 .
- Parfrey , P. , Foley , R. , Wittreich , B. et al. ( 2005 ). The Canadian European Study Group. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease . J. Am. Soc. Nephrol. 16 : 2180 – 2189 .
- Drueke , T.B. , Locatelli , F. , Clyne , N. et al. ( 2006 ). Normalization of hemoglobin level in patients with chronic kidney disease and anemia . N. Engl. J. Med. 355 : 2071 – 2084 .
- Singh , A.K. , Szczech , L. , Tang , K.L. et al. ( 2006 ). Correction of anemia with epoetin alfa in chronic kidney disease . N. Engl. J. Med. 355 : 2085 – 2098 .
- Pfeffer , M.A. , Burdmann , E.A. , Chen , C.Y. et al. ( 2009 ). The TREAT investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease . N. Engl. J. Med. 361 : 2019 – 2032 .
- Macdougall , I.C. , Provenzano , R. , Sharma , A. et al. ( 2013 ). Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis . N. Engl. J. Med. 368 : 320 – 332 .
- Fishbane , S. , Schiller , B. , Locatelli , F. et al. ( 2013 ). Peginesatide in patients with anemia undergoing hemodialysis . N. Engl. J. Med. 368 : 307 – 319 .
-
Macdougall , L.C.
,
White , C.
,
Anker , S.D.
et al. (
2018
).
Intravenous iron in patients undergoing maintenance hemodialysis
.
N. Engl. J. Med
.
https://doi.org/10.1056/NEJMoal1810742
.
10.1056/NEJMoal1810742 Google Scholar
- US Renal Data System ( 2014 ,). 2014 Annual Data Report: Atlas of End-Stage Renal Disease in the United States . Bethesda, MD : National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases .
- Parfrey , P.S. ( 2011 ). Critical appraisal of randomized controlled trials of anemia correction in patients with renal failure . Curr. Opin. Nephrol. Hypertens. 20 : 177 – 181 .
- Foley , R.N. , Curtis , B.M. , and Parfrey , P.S. ( 2008 ). Hemoglobin targets and blood transfusions in hemodialysis patients without symptomatic cardiac disease receiving erythropoietin therapy . Clin. J. Am. Soc. Nephrol. 3 : 1669 – 1675 .
- Solomon , S.D. , Uno , H. , Lewis , E.F. et al. ( 2010 ). Erythropoietic response and outcomes in kidney disease and type 2 diabetes . N. Engl. J. Med. 363 : 1146 – 1155 .
- Palmer , S.C. , Navaneethan , S.C. , Craig , J.C. et al. ( 2010 ). Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease . Ann. Intern. Med. 153 : 23 – 33 .
-
Palmer , S.C.
,
Saglimbene , V.
,
Craig , J.C.
et al. (
2014
).
Darbepoetin for the anaemia of chronic kidney disease
.
Cochrane Database Syst. Rev
. Art. No.: CD009297, doi:
https://doi.org/10.1002/14651858.CD009297
volume 3.
10.1002/14651858.CD009297 Google Scholar
- Palmer , S.C. , Saglimbene , V. , Mavridis , D. et al. ( 2014 ). Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis . Chochrane Database Syst. Rev. ( 12 ) Art. No.: CD 010590. doi: https://doi.org/10.1002/14651858.CD010590 .
- Saglimbene , V. , Palmer , S.C. , Ruospo , M. et al. ( 2017 ). Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease . Cochrane Database Syst. Rev. 8 Art. No.: CD009904. doi: https://doi.org/10.1002/14651858.CD009904 .
- Collister , D. , Komenda , P. , Hiebert , B. et al. ( 2016 ). The effect of erythropoietin-stimulating agents on health-related quality of life in anemia of chronic kidney disease: a systematic review and meta-analysis . Ann. Intern. Med. 164 : 472 – 478 .
- Foley , R.N. , Curtis , B.M. , and Parfrey , P.S. ( 2009 ). Erythropoietin therapy, hemoglobin targets, and quality of life in healthy hemodialysis patients: a randomized trial . Clin. J. Am. Soc. Nephrol. 4 : 726 – 733 .
- Lewis , E.F. , Pfeffer , M.A. , Feng , A. et al. ( 2011 ). Darbepoetin alfa impact on health status in diabetes patients with kidney disease: a randomized trial . Clin. J. Am. Soc. Nephrol. 6 : 845 – 855 .
- US Food and Drug Administration . Omontys (peginesatide) injection by affymax and takeda: recall of all lots – serious hypersensitivity reactions . http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts . (accessed 11 March 2013).
- Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group ( 2012 ). KDIGO clinical practice guideline for anemia in chronic kidney disease . Kidney Int. Suppl. 2 : 279 – 355 .
- Shepshelovich , D. , Rozen-Zvi , B. , Avni , T. et al. ( 2016 ). Intravenous versus oral iron supplementation for the treatment of anemia in CKD: an updated systematic review and meta-analysis . Am. J. Kidney Dis. 68 : 677 – 690 .
- Roger , S.D. , Tio , M. , Park , H.C. et al. ( 2017 ). Intravenous iron and erythropoiesis-stimulating agents in haemodialysis: a systematic review and meta-analysis . Nephrology (Carlton) 22 : 969 – 976 .
- Besarab , A. , Chernyavskaya , E. , Motylev , I. et al. ( 2016 ). Roxadustat (FG-4592): correction of anemia in incident dialysis patients . J. Am. Soc. Nephrol. 27 : 1225 – 1233 .
- Brigandi , R.A. , Johnson , B. , Oei , C. et al. ( 2016 ). A novel hypoxia-inducible factor-prolyl hydroxylase inhibitor (GSK1278863) for anemia in CKD; a 28-day, phase 2A randomized trial . Am. J. Kidney Dis. 67 : 861 – 871 .
- Pergola , P.E. , Spinowitz , B.S. , Hartman , C.S. et al. ( 2016 ). Vadudustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease . Kidney Int. 90 : 1115 – 1122 .
