Anemia in chronic kidney disease
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.
KeywordsHemoglobin Anemia Iron-restricted erythropoiesis Erythropoiesis-stimulating agent Hepcidin
MAA was supported by the National Institutes of Health (NIH)/NIDDK (K23-DK-084116).
Compliance with ethical standards
BAW is a consultant for Amgen, Inc.
- 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):878–888CrossRefPubMedPubMedCentralGoogle 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):665–676CrossRefPubMedPubMedCentralGoogle 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):1–156Google 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):51–54Google 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):3731–3737CrossRefPubMedGoogle 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–S146Google 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):843–852CrossRefPubMedGoogle 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):2019–2032CrossRefPubMedGoogle 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):1697–1703CrossRefPubMedPubMedCentralGoogle 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):861–871CrossRefPubMedGoogle 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):252–263CrossRefPubMedPubMedCentralGoogle 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 0:1–5Google Scholar