Skip to main content

Advertisement

Log in

Anemia in chronic kidney disease

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Anemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD progresses, but impaired production of erythropoietin by failing kidneys is a central cause. Hepcidin-mediated iron restriction also contributes to anemia by downregulating both intestinal iron absorption and release of stored iron for erythropoiesis. The core components of anemia management remain erythropoiesis-stimulating agents (ESA) and iron supplementation, but despite these therapies, a substantial number of children remain anemic. Although escalating ESA dose to target higher hemoglobin has been associated with adverse outcomes in adults, no trials have investigated this association in children, and maintaining hemoglobin levels in a narrow range with conservative ESA dosing is challenging. Judicious use of iron supplementation can enhance the response to ESAs, but the iron storage markers most commonly used in clinical practice have limitations in distinguishing which patients will benefit most from additional iron. Several novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl hydroxylase inhibitors, and dialysate-delivered iron supplements, have been developed and may offer options for alternative anemia management. However, the safety and efficacy of these agents in children with CKD has yet to be assessed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S (2006) Association of mortality and hospitalization with achievement of adult hemoglobin targets in adolescents maintained on hemodialysis. J Am Soc Nephrol 17(10):2878–2885

    Article  PubMed  Google Scholar 

  2. Schaefer F (2008) Cardiac disease in children with mild-to-moderate chronic kidney disease. Curr Opin Nephrol Hypertens 17(3):292–297

    Article  PubMed  Google Scholar 

  3. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2006) Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr 149(5):671–675

    Article  PubMed  Google Scholar 

  4. Atkinson MA, Martz K, Warady BA, Neu AM (2010) Risk for anemia in pediatric chronic kidney disease patients: a report of NAPRTCS. Pediatr Nephrol 25(9):1699–1706

    Article  PubMed  Google Scholar 

  5. Staples AO, Wong CS, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Greenbaum LA (2009) Anemia and risk of hospitalization in pediatric chronic kidney disease. Clin J Am Soc Nephrol 4(1):48–56

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fadrowski JJ, Pierce CB, Cole SR, Moxey-Mims M, Warady BA, Furth SL (2008) Hemoglobin decline in children with chronic kidney disease: baseline results from the chronic kidney disease in children prospective cohort study. Clin J Am Soc Nephrol 3(2):457–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Warady BA, Abraham AG, Schwartz GJ, Wong CS, Muñoz A, Betoko A, Mitsnefes M, Kaskel F, Greenbaum LA, Mak RH, Flynn J, Moxey-Mims MM, Furth S (2015) Predictors of rapid progression of glomerular and Nonglomerular kidney disease in children and adolescents: the chronic kidney disease in children (CKiD) cohort. Am J Kidney Dis 65(6):878–888

    Article  PubMed  PubMed Central  Google Scholar 

  8. Naito M, Kawashima A, Akiba T, Takanashi M, Nihei H (2003) Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming U-erythroid in chronic hemodialysis patients. Am J Nephrol 23(5):287–293

    Article  CAS  PubMed  Google Scholar 

  9. Borzych-Duzalka D, Bilginer Y, Ha IS, Bak M, Rees L, Cano F, Munarriz RL, Chua A, Pesle S, Emre S, Urzykowska A, Quiroz L, Ruscasso JD, White C, Pape L, Ramela V, Printza N, Vogel A, Kuzmanovska D, Simkova E, Müller-Wiefel DE, Sander A, Warady BA, Schaefer F, International Pediatric Peritoneal Dialysis Network (IPPN) Registry (2013) Management of anemia in children receiving chronic peritoneal dialysis. J Am Soc Nephrol 24(4):665–676

    Article  PubMed  PubMed Central  Google Scholar 

  10. Atkinson MA, Pierce CB, Zack RM, Barletta GM, Yadin O, Mentser M, Warady BA, Furth SL (2010) Hemoglobin differences by race in children with CKD. Am J Kidney Dis 55(6):1009–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Robins EB, Blum S (2007) Hematologic reference values for african american children and adolescents. Am J Hematol 82(7):611–614

    Article  CAS  PubMed  Google Scholar 

  12. Warady BA, Ho M (2003) Morbidity and mortality in children with anemia at initiation of dialysis. Pediatr Nephrol 18(10):1055–1062

    Article  PubMed  Google Scholar 

  13. Mitsnefes M, Flynn J, Cohn S, Samuels J, Blydt-Hansen T, Saland J, Kimball T, Furth S, Warady B, CKiD Study Group (2010) Masked hypertension associates with left ventricular hypertrophy in children with CKD. J Am Soc Nephrol 21(1):137–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Matteucci MC, Wühl E, Picca S, Mastrostefano A, Rinelli G, Romano C, Rizzoni G, Mehls O, de Simone G, Schaefer F, ESCAPE Trial Group (2006) Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol 17(1):218–226

    Article  PubMed  Google Scholar 

  15. Gerson A, Hwang W, Fiorenza J, Barth K, Kaskel F, Weiss L, Zelikovsky N, Fivush B, Furth S (2004) Anemia and health-related quality of life in adolescents with chronic kidney disease. Am J Kidney Dis 44(6):1017–1023

    Article  PubMed  Google Scholar 

  16. Yabu JM, Anderson MW, Kim D, Bradbury BD, Lou CD, Petersen J, Rossert J, Chertow GM, Tyan DB (2013) Sensitization from transfusion in patients awaiting primary kidney transplant. Nephrol Dial Transplant 28(11):2908–2918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Obrador GT, Macdougall IC (2013) Effect of red cell transfusions on future kidney transplantation. Clin J Am Soc Nephrol 8(5):852–860

    Article  PubMed  Google Scholar 

  18. Hollowell JG, van Assendelft OW, Gunter EW, Lewis BG, Najjar M, Pfeiffer C, Centers for Disease Control and Prevention, National Center for Health Statistics (2005) Hematological and iron-related analytes--reference data for persons aged 1 year and over: United states, 1988-94. Vital Health Stat 11(247):1–156

    Google Scholar 

  19. Jackson RT (1990) Separate hemoglobin standards for blacks and whites: a critical review of the case for separate and unequal hemoglobin standards. Med Hypotheses 32(3):181–189

    Article  CAS  PubMed  Google Scholar 

  20. Filler G, Mylrea K, Feber J, Wong H (2007) How to define anemia in children with chronic kidney disease? Pediatr Nephrol 22(5):702–707

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  22. Foley RN (2008) Erythropoietin: physiology and molecular mechanisms. Heart Fail Rev 13:405–414

    Article  CAS  PubMed  Google Scholar 

  23. Koury MJ, Haase VH (2015) Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol 11:394–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Donnelly S (2001) Why is erythropoietin made in the kidney? The kidney functions as a Critmeter. Am J Kid Dis 38(2):415–425

    Article  CAS  PubMed  Google Scholar 

  25. Locatelli F, Fishbane S, Block GA, Macdougall IC (2017) Targeting hypoxia-inducible factors for the treatment of anemia in chronic kidney disease Pateints. Am J Nephrol 45(3):187–199

    Article  CAS  PubMed  Google Scholar 

  26. Sangkhae V, Nemeth E (2017) Regulation of the iron homeostatic hormone Hepcidin. Adv Nutr 8(1):126–136

    Article  PubMed  PubMed Central  Google Scholar 

  27. Camaschella C, Pagani A, Nai A, Silvestri L (2016) The mutual control of iron and erythropoiesis. Int J Lab Hematol 38S1:20–26

    Article  Google Scholar 

  28. Goodnough LT, Nemeth E, Ganz T (2010) Detection, evaluation, and management of iron-restricted erythropoiesis. Blood 116(23):4754–4761

    Article  CAS  PubMed  Google Scholar 

  29. Greenbaum LA (2005) Anemia in children with chronic kidney disease. Adv Chronic Kidney Dis 12(4):385–396

    Article  PubMed  Google Scholar 

  30. Atkinson MA, Furth SL (2011) Anemia in children with chronic kidney disease. Nat Rev Nephrol 7(11):635–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Poli M, Asperti M, Ruzzenenti P, Regoni M, Arosio P (2014) Hepcidin antagonists for potential treatments of disorders with hepcidin excess. Front Pharmacol 5:86

    Article  PubMed  PubMed Central  Google Scholar 

  32. Atkinson MA, White CT (2012) Hepcidin in anemia of chronic kidney disease: review for the pediatric nephrologist. Pediatr Nephrol 27(1):33–40

    Article  PubMed  Google Scholar 

  33. Ganz T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102(3):783–788

    Article  CAS  PubMed  Google Scholar 

  34. Atkinson MA, Kim JY, Roy CN, Warady BA, White CT, Furth SL (2015) Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol 30(4):635–643

    Article  PubMed  Google Scholar 

  35. Zaritsky J, Young B, Wang HJ, Westerman M, Olbina G, Nemeth E, Ganz T, Rivera S, Nissenson AR, Salusky IB (2009) Hepcidin--a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 4(6):1051–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zaritsky J, Young B, Gales B, Wang HJ, Rastogi A, Westerman M, Nemeth E, Ganz T, Salusky IB (2010) Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. Clin J Am Soc Nephrol 5(6):1010–1014

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, Nayak A, Wesseling-Perry K, Westerman M, Hollis BW, Saluskt IB, Hewison M (2014) J Am Soc Nephrol 25(3):564–572

    Article  CAS  PubMed  Google Scholar 

  38. Atkinson MA, Juraschek SP, Bertenthal MS, Detrick B, Furth SL, Miller ER 3rd (2016) Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease. Pediatr Nephrol. doi:10.1007/s00467-016-3563-6

    PubMed  PubMed Central  Google Scholar 

  39. Nangaku M, Eckardt KU (2006) Pathogenesis of renal anemia. Semin Nephrol 26(4):261–268

    Article  CAS  PubMed  Google Scholar 

  40. Koshy SM, Geary DF (2008) Anemia in children with chronic kidney disease. Pediatr Nephrol 23(2):209–219

    Article  PubMed  Google Scholar 

  41. Rao DS, Shih MS, Mohini R (1993) Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med 328(3):171–175

    Article  CAS  PubMed  Google Scholar 

  42. Chutia H, Ruram AA, Bhattacharyya H, Boruah P, Nath C (2013) Association of secondary hyperparathyroidism with hemoglobin level in patients with chronic kidney disease. J Lab Phys 5(1):51–54

    CAS  Google Scholar 

  43. Yorgin PD, Zaritsky J (2012) Management of Renal Anemia in children with chronic kidney disease. In: Warady BA, Schaefer F, Alexander SA (eds) Pediatric dialysis, 2nd edn. Springer, New York, pp 531–568

    Chapter  Google Scholar 

  44. Bamgbola O, Kaskel F (2005) Role of folate deficiency on erythropoietin resistance in pediatric and adolescent patients on chronic dialysis. Pediatr Nephrol 20(11):1622–1629

    Article  PubMed  Google Scholar 

  45. Calo LA, Vertolli U, Davis PA, Savica V (2012) L carnitine in hemodialysis patients. Hemodial Int 16(3):428–434

    Article  PubMed  Google Scholar 

  46. Raimann JG, Levin NW, Craig RG, Sirover W, Kotanko P, Handelman G (2013) Is vitamin C intake too low in dialysis patients? Semin Dial 26(1):1–5

    Article  PubMed  Google Scholar 

  47. Nasr SH, Kashtanova Y, Levchuk V, Markowitz GS (2006) Secondary oxalosis due to excessive vitamin C intake. Kidney Int 70(10):1672

    Article  CAS  PubMed  Google Scholar 

  48. Lazarchick J (2012) Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol 19(1):58–60

    Article  CAS  PubMed  Google Scholar 

  49. Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med 316(2):73–78

    Article  CAS  PubMed  Google Scholar 

  50. Covic A, Cannata-Andia J, Cancarini G, Coppo R, Frazão JM, Goldsmith D, Ronco P, Spasovski GB, Stenvinkel P, Utas C, Wiecek A, Zoccali C, London G (2008) Biosimilars and biopharmaceuticals: what the nephrologists need to know--a position paper by the ERA-EDTA council. Nephrol Dial Transplant 23(12):3731–3737

    Article  PubMed  Google Scholar 

  51. Horl WH (2013) Differentiating factors between erythropoiesis-stimulating agents: an update to selection for anaemia of chronic kidney disease. Drugs 73(2):117–130

    Article  PubMed  Google Scholar 

  52. Warady BA, Arar MY, Lerner G, Nakaniski AM, Stehman-Breen C (2006) Darbepoetin alfa for the treatment of anemia in pediatric patients with chronic kidney disease. Pediatr Nephrol 21(8):1144–1152

    Article  PubMed  Google Scholar 

  53. Anemia in Chronic Kidney Disease Work Group (2006) KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 47(Supplement 3):S1–S146

  54. Schaefer F, Hoppe B, Jungraithmayr T, Klaus G, Pape L, Farouk M, Addison J, Manamley N, Vondrak K (2016) Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study. Pediatr Nephrol 31:443–453

    Article  PubMed  Google Scholar 

  55. Schmitt CP, Nau B, Brummer C, Rosenkranz J, Schaefer F (2006) Increased injection pain with darbepoetin-alpha compared with epoetin-beta in paediatric dialysis patients. Nephrol Dial Transplant 21(12):3520–3524

    Article  CAS  PubMed  Google Scholar 

  56. Wish JB, Charytan C, Chertow GM, Kalantar-Zadeh K, Kliger AS, Rubin RJ, Yee J, Fishbane S (2016) Introduction of biosimilar therapeutics into Nephrology practice in the United States: report of a scientific workshop sponsored by the National Kidney Foundation. Am J Kidney Dis 68(6):843–852

    Article  PubMed  Google Scholar 

  57. Cano F, Alarcon C, Azocar M, Lizama C, Lillo AM, Delucchi A, Gonzalez M, Arellano P, Delgado I, Droguett MT (2011) Continuous EPO receptor activator therapy of anemia in children under peritoneal dialysis. Pediatr Nephrol 26(8):1303–1310

    Article  PubMed  Google Scholar 

  58. Warady MA, Ho M (2003) Morbidity and mortality in children with anemia at initiation of dialysis. Pediatr Nephrol 18(10):1055–1062

    Article  PubMed  Google Scholar 

  59. Bamgbola OF, Kaskel FJ, Coco M (2009) Analyses of age, gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts. Pediatr Nephrol 24(3):571–579

    Article  PubMed  Google Scholar 

  60. Port RE, Kiepe D, Van Guilder M, Jelliffe RW, Mehls O (2004) Recombinant human erythropoietin for the treatment of renal anaemia in children: no justification for bodyweight-adjusted dosage. Clin Pharmacokinet 43(1):57–70

    Article  CAS  PubMed  Google Scholar 

  61. Port RE, Mehls O (2009) Erythropoietin dosing in children with chronic kidney disease: based on body size or on hemoglobin deficit? Pediatr Nephrol 24(3):435–437

    Article  PubMed  Google Scholar 

  62. McGowan T, Vaccaro NM, Beaver JS, Massarella J, Wolfson M (2008) Pharmacokinetic and Pharmacodynamic profiles of extended dosing of Epoetin alfa in anemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol 3:1006–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pergola PE, Gartenberg G, Fu M, Sun S, Wolfson M, Bowers P (2010) A randomized controlled study comparing once-weekly to every-2-week and every-4-week dosing of Epoetin alfa in CKD patients with anemia. Clin J Am Soc Nephrol 5:598–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fishbane S, Berns JS (2005) Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin. Kidney Int 68(3):1337–1343

    Article  CAS  PubMed  Google Scholar 

  65. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D, Investigators CHOIR (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098

    Article  CAS  PubMed  Google Scholar 

  66. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R, Investigators TREAT (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361(21):2019–2032

    Article  PubMed  Google Scholar 

  67. Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L (2013) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 62(5):849–859

    Article  PubMed  Google Scholar 

  68. Badve SV, Hawley CM, Johnson DW (2011) Is the problem with the vehicle or the destination? Does high-dose ESA or high haemoglobin contribute to poor outcomes in CKD? Nephrology (Carlton) 16(2):144–153

    Article  Google Scholar 

  69. Goodkin DA, Fuller DS, Robinson BM, Combe C, Fluck R, Mendelssohn D, Akizawa T, Pisoni RL, Port FK (2011) Naturally occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients. J Am Soc Nephrol 22(2):358–365

    Article  PubMed  PubMed Central  Google Scholar 

  70. Unger EF, Thompson AM, Blank MJ, Temple R (2010) Erythropoiesis-stimulating agents--time for a reevaluation. N Engl J Med 362(3):189–192

    Article  CAS  PubMed  Google Scholar 

  71. Lestz RM, Fivush BA, Atkinson MA (2014) Association of higher erythropoiesis stimulating agent dose and mortality in children on dialysis. Pediatr Nephrol 29(10):2021–2028

    Article  PubMed  PubMed Central  Google Scholar 

  72. Pollock C, Johnson DW, Horl WH, Rossert J, Casadevall N, Schellenkens H, Delage R, De Francisco A, Macdougall I, Thorpe R, Toffelmire E (2008) Pure red cell aplasia induced by erythropoiesis-stimulating agents. Clin J Am Soc Nephrol 3(1):193–199

    Article  CAS  PubMed  Google Scholar 

  73. Bennett CL, Starko KM, Thomsen HS, Cowper S, Sartor O, Macdougall IC, Qureshi ZP, Bookstaver PB, Miller AD, Norris LB, Xirasagar S, Trenery A, Lopez I, Kahn A, Murday A, Luminari S, Cournoyer D, Locatelli F, Ray P, Mattison DR (2012) Linking drugs to obscure illnesses: lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and reye’s syndrome. A report from the southern network on adverse reactions (SONAR). J Gen Intern Med 27(12):1697–1703

    Article  PubMed  PubMed Central  Google Scholar 

  74. Babitt JL, Lin HY (2012) Mechanisms of anemia in CKD. J Am Soc Nephrol 23(10):1631–1634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Atkinson MA, Pierce CB, Fadrowski JJ, Benador NM, White CT, Turman MA, Pan CG, Abraham AG, Warady BA, Furth SL (2012) Association between common iron store markers and hemoglobin in children with chronic kidney disease. Pediatr Nephrol 27(12):2275–2283

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kalantar-Zadeh K, Kalantar-Zadeh K, Lee GH (2006) The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease? Clin J Am Soc Nephrol Suppl 1:9–18

    Article  Google Scholar 

  77. Davidkova S, Prestidge TD, Reed PW, Kara T, Wong W, Prestidge C (2016) Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. Pediatr Nephrol 31(5):819–826

    Article  PubMed  Google Scholar 

  78. Charytan DM, Pai AB, Chan CT, Coyne DW, Hung AM, Kovesdy CP, Fishbane S, Dialysis Advisory Group of the American Society of Nephrology (2015) Considerations and challenges in defining optimal iron utilization in hemodialysis. J Am Soc Nephrol 26(6):1238–1247

    Article  CAS  PubMed  Google Scholar 

  79. Anirban G, Kohli HS, Jha V, Gupta KL, Sakhuja V (2008) The comparative safety of various intravenous iron preparations in chronic kidney disease patients. Ren Fail 30(6):629–638

    Article  CAS  PubMed  Google Scholar 

  80. Ishida JH, Marafino MJ, McCulloch CE, Dalrymple LS, Dudley RA, Grimes BA, Johansen KL (2015) Receipt of intravenous iron and clinical outcomes among hemodialysis patients hospitalized for infection. Clin J Am Soc Nephrol 10(10):1799–1805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Warady BA, Kausz A, Lerner G, Brewer ED, Chadha V, Brugnara C, Dahl NV, Watkins SL (2004) Iron therapy in the pediatric hemodialysis population. Pediatr Nephrol 19(6):655–661

    Article  PubMed  Google Scholar 

  82. Warady BA, Zobrist RH, Wu J, Finan E, Ferrlecit Pediatric Study Group (2005) Sodium ferric gluconate complex therapy in anemic children on hemodialysis. Pediatr Nephrol 20(9):1320–1327

    Article  PubMed  Google Scholar 

  83. Goldstein SL, Morris D, Warady BA (2013) Comparison of the safety and efficacy of 3 iron sucrose iron maintenance regimens in children, adolescents, and young adults with CKD: a randomized controlled trial. Am J Kidney Dis 61(4):588–597

    Article  CAS  PubMed  Google Scholar 

  84. Brigandi RA, Johnson B, Oei C, Westerman M, Olbina G, de Zoysa J, Roger SD, Sahay M, Cross N, McMahon L, Guptha V, Smolyarchuk EA, Singh N, Russ SF, Kumar S on behalf of the PHI112844 Investigators (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(6):861–871

    Article  CAS  PubMed  Google Scholar 

  85. Besarab A, Chernyavskaya E, Motylev I, Shutov E, Kumbar LM, Gurevich K, Chan DTM, Leong R, Poole L, Zhong M, Saikali KG, Franco M, Hemmerich S, Yu K-HP, Neff TB (2016) Roxadustat (FG-4592): correction of anemia in incident dialysis patients. J Am Soc Nephrol 27:1225–1233

    Article  CAS  PubMed  Google Scholar 

  86. Schmid H, Jelkmann W (2016) Investigational therapies for renal disease-induced anemia. Expert Opin Investig Drugs 25(8):901–916

    Article  CAS  PubMed  Google Scholar 

  87. Cooke KS, Hinkle B, Salimi-Moosavi H, Foltz I, King C, Rathanaswami P, Winters A, Steavenson S, Begley CG, Molineux G, Sasu BJ (2013) A fully human antihepcidin antibody modulates iron metabolism in both mice and nonhuman primates. Blood 122(17):3054–3061

    Article  CAS  PubMed  Google Scholar 

  88. Shah HH, Hazzan AD, Fishbane S (2016) Ferric pyrophosphate citrate: a novel iron replacement agent in patients undergoing hemodialysis. Semin Nephrol 36(2):124–129

    Article  CAS  PubMed  Google Scholar 

  89. Yagil Y, Fadem SZ, Kant KS, Bhatt U, Sika M, Lewis JB, Negoi D, for the Collaborative Study Group (2015) Managing hyperphosphatemia in patients with chronic kidney disease on dialysis with ferric citrate: latest evidence and clinical usefulness. Ther Adv Chronic Dis 6(5):252–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Gilbertson DT, Peng Y, Arneson TJ, Dunning S, Collins AJ (2013) Comparison of methodologies to define hemodialysis patients hyporesponsive to epoetin and impact on counts and characteristics. BMC Nephrol 14:44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bamgbola O (2012) Resistance to erythropoietin-stimulating agents: etiology, evaluation, and therapeutic considerations. Pediatr Nephrol 27(2):195–205

    Article  PubMed  Google Scholar 

  92. Bamgbola O (2016) Spectrum of anemia after kidney transplantation: pathophysiology and therapeutic implications. Clin Transpl 30:1185–1194

    Article  CAS  Google Scholar 

  93. Krause I, Davodovits M, Tamary H, Yutcis M, Dagan A (2016) Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared with children with chronic renal failure 2016. Pediatr Transplant 0:1–5

  94. Jacobson PA, Schladt D, Oetting WS, Leduc R, Guan W, Matas AJ, Lamba V, Mannon RB, Julian BA, Israni A, Investigators DKAF (2011) Genetic determinants of mycophenolate-related anemia and leukopenia after transplantation. Transplantation 91(3):309–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

MAA was supported by the National Institutes of Health (NIH)/NIDDK (K23-DK-084116).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Meredith A. Atkinson.

Ethics declarations

Disclosures

BAW is a consultant for Amgen, Inc.

Additional information

Answers to questions:

1. b

2. c

3. d

4. a

5. c

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Atkinson, M.A., Warady, B.A. Anemia in chronic kidney disease. Pediatr Nephrol 33, 227–238 (2018). https://doi.org/10.1007/s00467-017-3663-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-017-3663-y

Keywords

Navigation