Main Article Content

Abstract

CKD anaemia, commonly referred to as anaemia of chronic renal disease, is a subtype of hypoproliferative anaemia and normocytic normochromic anaemia.  This condition is prevalent among people with renal illness and is linked to poor outcomes and a higher risk of death in CKD patients.  While there are many similarities between it and the chronic inflammatory elements of CKD anaemia, a significant difference is that CKD anaemia is characterised by a severe erythropoietin shortage.  Therefore, the goal of treatment is to increase the generation of red blood cells, decrease functional iron shortage, and improve renal function wherever possible.  A full blood count with differential, peripheral smear, and tests to rule out other causes of anaemia, such as B12, folate, haptoglobin, thyroid studies, and iron indices (iron, ferritin, total iron-binding capacity, saturation of transferrin and folate), are necessary for the diagnosis. Iron supplements and erythropoiesis-stimulating agents (ESAs) are presently the mainstays of treatment for anaemia associated with chronic renal illness.  Since the first ESA and intravenous iron formulations were used, guidelines have changed considerably, and numerous novel therapeutic approaches are now on the market or being investigated in advanced-phase clinical trials.  The assessment and treatment of anaemia in chronic renal illness are reviewed in this activity.  In order to provide the best possible care for those impacted by this illness, this activity also emphasises the need of the interprofessional healthcare team.

Keywords

Anemia Chronic kidney disease Erythropoiesis stimulating agents

Article Details

How to Cite
Chiluka Purvi, Chelle Laxmiprasanna, Dara Harika, Cheganti Rahul, Chethireddy Rajasimha, Pratap devi shankar sai prakash, & Meesala Gowthami. (2025). CKD-Induced Anemia Revisited: Interplay of inflammation, Iron, and Novel Therapies. International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(3), 269-276. https://doi.org/10.61096/ijrpp.v14.iss3.2025.269-276

References

  1. 1. Badura K, Janc J, Wąsik J, Gnitecki S, Skwira S, Młynarska E, Rysz J, Franczyk B. Anemia of Chronic Kidney Disease-A Narrative Review of Its Pathophysiology, Diagnosis, and Management. Biomedicines. 2024 May 27;12(6) .
  2. 2. Babitt JL, Eisenga MF, Haase VH, Kshirsagar AV, Levin A, Locatelli F, Małyszko J, Swinkels DW, Tarng DC, Cheung M, Jadoul M, Winkelmayer WC, Drüeke TB., Conference Participants. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2021 Jun;99(6):1280-1295.
  3. 3. Cases and Observations Illustrative of Renal Disease, Accompanied with the Secretion of Albuminous Urine. Med Chir Rev. 1836 Jul 01;25(49):23-35.
  4. 4. Fishbane S, Coyne DW. How I treat renal anemia. Blood. 2020 Aug 13;136(7):783-789.
  5. 5. DeGowin RL, Lavender AR, Forland M, Charleston D, Gottschalk A. Erythropoiesis and erythropoietin in patients with chronic renal failure treated with hemodialysis and testosterone. Ann Intern Med. 1970 Jun;72(6):913-8.
  6. 6. Richardson JR, Weinstein MB. Erythropoietic response of dialyzed patients to testosterone administration. Ann Intern Med. 1970 Sep;73(3):403-7.
  7. 7. 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 Jan 08;316(2):73-8.
  8. 8. Macdougall IC, Lewis NP, Saunders MJ, Cochlin DL, Davies ME, Hutton RD, Fox KA, Coles GA, Williams JD. Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. Lancet. 1990 Mar 03;335(8688):489-93.
  9. 9. Charytan DM, Pai AB, Chan CT, Coyne DW, Hung AM, Kovesdy CP, Fishbane S., Dialysis Advisory Group of the American Society of Nephrology. Considerations and challenges in defining optimal iron utilization in hemodialysis. J Am Soc Nephrol. 2015 Jun;26(6):1238-47.
  10. 10. Coyne DW. The health-related quality of life was not improved by targeting higher hemoglobin in the Normal Hematocrit Trial. Kidney Int. 2012 Jul;82(2):235-41.
  11. 11. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, Günzler V, Eckardt KU. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010 Dec;21(12):2151-6.
  12. 12. 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 U S A. 1995 Jun 06;92(12):5510-4.
  13. 13. Agarwal AK. Practical approach to the diagnosis and treatment of anemia associated with CKD in elderly. J Am Med Dir Assoc. 2006 Nov;7(9 Suppl):S7-S12; quiz S17-21. [PubMed]
  14. 14. Batchelor EK, Kapitsinou P, Pergola PE, Kovesdy CP, Jalal DI. Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment. J Am Soc Nephrol. 2020 Mar;31(3):456-468. [PMC free article] [PubMed]
  15. 15. Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest. 2007 Jul;117(7):1933-9. [PMC free article] [PubMed]
  16. 16. Nakai T, Iwamura Y, Kato K, Hirano I, Matsumoto Y, Tomioka Y, Yamamoto M, Suzuki N. Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice. Blood Adv. 2023 Aug 08;7(15):3793-3805. [PMC free article] [PubMed]
  17. 17. St Peter WL, Guo H, Kabadi S, Gilbertson DT, Peng Y, Pendergraft T, Li S. Prevalence, treatment patterns, and healthcare resource utilization in Medicare and commercially insured non-dialysis-dependent chronic kidney disease patients with and without anemia in the United States. BMC Nephrol. 2018 Mar 15;19(1):67. [PMC free article] [PubMed]
  18. 18. Inker LA, Grams ME, Levey AS, Coresh J, Cirillo M, Collins JF, Gansevoort RT, Gutierrez OM, Hamano T, Heine GH, Ishikawa S, etal., CKD Prognosis Consortium. Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis. 2019 Feb;73(2):206-217. [PMC free article] [PubMed]
  19. 19. KDOQI; National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006 May;47(5 Suppl 3):S11-145. [PubMed]
  20. 20. Eschbach JW. The anemia of chronic renal failure: pathophysiology and the effects of recombinant erythropoietin. Kidney Int. 1989 Jan;35(1):134-48. [PubMed]
  21. 21. Vos FE, Schollum JB, Coulter CV, Doyle TC, Duffull SB, Walker RJ. Red blood cell survival in long-term dialysis patients. Am J Kidney Dis. 2011 Oct;58(4):591-8. [PubMed]
  22. 22. Park MY, Le Henaff C, Sitara D. Administration of α-Klotho Does Not Rescue Renal Anemia in Mice. Front Pediatr. 2022;10:924915. [PMC free article] [PubMed]
  23. 23. Carrera F, Burnier M. Use of darbepoetin alfa in the treatment of anaemia of chronic kidney disease: clinical and pharmacoeconomic considerations. NDT Plus. 2009 Jan;2(Suppl_1):i9-i17. [PMC free article] [PubMed]
  24. 24. Fishbane S, Singh B, Kumbhat S, Wisemandle WA, Martin NE. Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease. Clin J Am Soc Nephrol. 2018 Aug 07;13(8):1204-1214. [PMC free article] [PubMed]
  25. 25. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, Locatelli F, Dougherty FC, Beyer U., ARCTOS Study Investigators. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol. 2008 Mar;3(2):337-47. [PMC free article] [PubMed]
  26. 26. Szczech LA, Barnhart HX, Inrig JK, Reddan DN, Sapp S, Califf RM, Patel UD, Singh AK. Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int. 2008 Sep;74(6):791-8. [PMC free article] [PubMed]
  27. 27. Fishbane S, Berns JS. Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin. Kidney Int. 2005 Sep;68(3):1337-43. [PubMed]
  28. 28. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke MJ, Weingart O, Kluge S, Piper M, Napoli M, Rades D, Steensma D, Djulbegovic B, Fey MF, Ray-Coquard I, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A. Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data. Cochrane Database Syst Rev. 2009 Jul 08;2009(3):CD007303. [PMC free article] [PubMed]
  29. 29. Badiu I, Diena D, Guida G, Ferrando C, Rapezzi D, Besso L. Cutaneous allergic reaction correlates with anti-erythropoietin antibodies in dialysis patient developing pure red cell aplasia. Clin Case Rep. 2022 Apr;10(4):e05554. [PMC free article] [PubMed]
  30. 30. Fudin R, Jaichenko J, Shostak A, Bennett M, Gotloib L. Correction of uremic iron deficiency anemia in hemodialyzed patients: a prospective study. Nephron. 1998;79(3):299-305. [PubMed]
  31. 31. 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 Nov 30;18(1):345. [PMC free article] [PubMed]
  32. 32. Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, Thomsen LL, Carpenter TO, Weber T, Brandenburg V, Zoller H. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA. 2020 Feb 04;323(5):432-443. [PMC free article] [PubMed]
  33. 33. Pergola PE, Fishbane S, Ganz T. Novel Oral Iron Therapies for Iron Deficiency Anemia in Chronic Kidney Disease. Adv Chronic Kidney Dis. 2019 Jul;26(4):272-291. [PubMed]
  34. 34. Fishbane SN, Singh AK, Cournoyer SH, Jindal KK, Fanti P, Guss CD, Lin VH, Pratt RD, Gupta A. Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients. Nephrol Dial Transplant. 2015 Dec;30(12):2019-26. [PMC free article] [PubMed]
  35. 35. Ziltivekimab is a human immunoglobulin G (IgG) monoclonal antibody that targets the inflammatory cytokine interleukin (IL)-6. When compared to a placebo, ziltivekimab has been shown to elevate albumin and haemoglobin levels, decrease inflammation, and enhance iron indices in patients with CKD stages 3 to 5. IL-6 is linked to elevated hepcidin expression, which could account for Ziltivekimab's therapeutic.