Treatment Options for Anemia in Kidney Transplant Patients: A Review

Abstract

Anemia is common after kidney transplantation. The etiology may be multifactorial, such as causes of anemia in the general population and causes that are unique to the kidney transplant setting. Posttransplant anemia, particularly when severe, may be associated with adverse effects such as graft failure, mortality, and a decline in kidney function. After careful investigation, that is, having excluded or treated reversible causes of anemia, treatment of anemia in patients with a kidney transplant is based on iron supplementation or erythropoiesis-stimulating agents (ESA), although there are no specific guidelines on anemia management in this patient population. Iron therapy is often needed, but optimal and safe iron-deficiency management strategies remain to be defined. Evidence suggests that ESAs are safe and potentially associated with favorable outcomes. Better graft function has been reported with ESA use targeting hemoglobin levels higher than those recommended in the general population with chronic kidney disease and with no apparent increased risk of cardiovascular events. These results require further investigation. Data on the use of hypoxia-inducible factor inhibitors are limited. Prevention and treatment of anemia in kidney transplantation can improve patients’ quality of life, life expectancy, allograft function, and survival. Anemia is common after kidney transplantation. The etiology may be multifactorial, such as causes of anemia in the general population and causes that are unique to the kidney transplant setting. Posttransplant anemia, particularly when severe, may be associated with adverse effects such as graft failure, mortality, and a decline in kidney function. After careful investigation, that is, having excluded or treated reversible causes of anemia, treatment of anemia in patients with a kidney transplant is based on iron supplementation or erythropoiesis-stimulating agents (ESA), although there are no specific guidelines on anemia management in this patient population. Iron therapy is often needed, but optimal and safe iron-deficiency management strategies remain to be defined. Evidence suggests that ESAs are safe and potentially associated with favorable outcomes. Better graft function has been reported with ESA use targeting hemoglobin levels higher than those recommended in the general population with chronic kidney disease and with no apparent increased risk of cardiovascular events. These results require further investigation. Data on the use of hypoxia-inducible factor inhibitors are limited. Prevention and treatment of anemia in kidney transplantation can improve patients’ quality of life, life expectancy, allograft function, and survival. Normocytic normochromic anemia represents a frequent complication in patients experiencing chronic kidney disease (CKD) and is associated with several adverse clinical outcomes.1Bonomini M. Del Vecchio L. Sirolli V. Locatelli F. New treatment approaches for the anemia of CKD.Am J Kidney Dis. 2016; 67: 133-142https://doi.org/10.1053/j.ajkd.2015.06.030Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar A successful kidney transplantation (KT) may potentially correct anemia. However, ∼20%-51% of kidney transplant recipients (KTRs) are anemic at various time points after transplantation.2Schechter A. Gafter-Gvili A. Shepshelovich D. et al.Post renal transplantation anemia: causes, severity and their association with graft and patient survival.BMC Nephrol. 2019; 20: 51https://doi.org/10.1186/s12882-019-1244-yCrossref PubMed Scopus (21) Google Scholar, 3Winkelmayer W.C. Chandraker A. Alan Brookhart M. Kramar R. Sunder-Plassmann G. A prospective study of anaemia and long-term outcomes in kidney transplant recipients.Nephrol Dial Transplant. 2006; 21: 3559-3566Crossref PubMed Scopus (57) Google Scholar, 4Gafter-Gvili A. Ayalon-Dangur I. Cooper L. et al.Posttransplantation anemia in kidney transplant recipients: a retrospective cohort study.Medicine. 2017; 96e7735https://doi.org/10.1097/MD.0000000000007735Crossref PubMed Scopus (19) Google Scholar Posttransplant anemia is usually differentiated into early and late. Early anemia (≤6 months after transplantation) has a prevalence of ∼50%, whereas late anemia occurs after 6 months in 23%-35% of patients who underwent transplantation.5Gafter-Gvili A. Gafter U. Posttransplantation anemia in kidney transplant recipients.Acta Haematol. 2019; 142: 37-43https://doi.org/10.1159/000496140Crossref PubMed Scopus (17) Google Scholar,6Malyszko J. Basak G. Batko K. et al.Haematological disorders following kidney transplantation.Nephrol Dial Transplant. 2022; 37: 409-420https://doi.org/10.1093/ndt/gfaa219Crossref PubMed Scopus (1) Google Scholar Posttransplant anemia is associated with reduced exercise capacity, cognitive decline, chronic fatigue, and impairment in quality of life.7Kawada N. Moriyama T. Ichimaru N. et al.Negative effects of anemia on quality of life and its improvement by complete correction of anemia by administration of recombinant human erythropoietin in posttransplant patients.Clin Exp Nephrol. 2009; 13: 355-360Crossref PubMed Scopus (13) Google Scholar,8Molina M. Sorolla C. Samsò E. et al.Quality of life in long-term renal transplant patients: a controversial subject.Transplant Proc. 2022; 54: 91-93https://doi.org/10.1016/j.transproceed.2021.11.025Crossref PubMed Scopus (0) Google Scholar Moreover, a growing number of observations indicate that anemia can be negatively associated with long-term clinical outcomes in KT, such as graft failure, mortality, and a decline in kidney function. Thus, it is reasonable to treat anemia in KTRs, probably starting as soon as possible after transplantation,5Gafter-Gvili A. Gafter U. Posttransplantation anemia in kidney transplant recipients.Acta Haematol. 2019; 142: 37-43https://doi.org/10.1159/000496140Crossref PubMed Scopus (17) Google Scholar although there are no proper or accurate guidelines for the management of anemia in this patient population. The KDIGO guidelines for KTRs9Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work GroupKDIGO Clinical Practice Guideline for the care of kidney transplant recipients.Am J Transplant. 2009; 9: S1-S157PubMed Google Scholar and the position statement from the European Renal Best Practice Group10Locatelli F. Covic A. Eckardt K.-U. Wiecek A. Vanholder R. ERA-EDTA ERBP advisory boardAnaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP).Nephrol Dial Transplant. 2009; PubMed Scopus Google Scholar anemia in by following the management guidelines for anemia in The of this to on posttransplant anemia in Anemia in has been Anemia after kidney transplantation. Nephrol. Scholar and be in this are causes of posttransplant anemia of Anemia in Kidney anemia and and graft and and anemia and and graft and and function with the prevalence and severity of C. et and management of anemia in renal transplant recipients: a European J Transplant. Full Text Full Text PDF PubMed Scopus Google N. et al.Posttransplantation anemia in renal allograft recipients: prevalence and 2006; PubMed Scopus Google Scholar erythropoietin by the graft occurs a of although it to a of on the of kidney M. E. et erythropoietin levels of renal transplant recipients the early Proc. PubMed Google Scholar levels may in to the kidney function N. A. Covic A. D. Anemia after renal J Kidney Dis. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar with the decline in the of the N. et al.Posttransplantation anemia in renal allograft recipients: prevalence and 2006; PubMed Scopus Google Scholar and levels are associated with graft N. A. Covic A. D. Anemia after renal J Kidney Dis. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar A in levels can be of A. J. G. of following renal Full Text PDF PubMed Google Scholar a may be in the of posttransplant anemia, to risk or or in the posttransplant or N. A. Covic A. D. Anemia after renal J Kidney Dis. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar Iron is in and may to early and late anemia. iron of increased by the and use of of the and may iron Iron after kidney transplantation.Nephrol Dial Transplant. PubMed Scopus Google Scholar and the use of of inhibitors the of to reduced iron iron for Iron after kidney transplantation.Nephrol Dial Transplant. PubMed Scopus Google Scholar and can be of erythropoietin and correction of anemia in kidney transplant Transplant. Google Scholar may the risk of anemia by or effects such as increased disorders after PubMed Scopus Google V. The for anaemia after kidney PubMed Scopus (0) Google Scholar The time of disease is usually in the months after transplant is with the therapy that V. et in the after renal Google Scholar However, by a in the may as early as after R. et in kidney transplant recipients: A prospective study in a in 2022; PubMed Scopus (0) Google Scholar anemia may be when are C. et and management of anemia in renal transplant recipients: a European J Transplant. Full Text Full Text PDF PubMed Scopus Google to anemia in recipients of has been A. of and anaemia after a 2022; PubMed Scopus (0) Google Scholar and and and or the J. Basak G. Batko K. et al.Haematological disorders following kidney transplantation.Nephrol Dial Transplant. 2022; 37: 409-420https://doi.org/10.1093/ndt/gfaa219Crossref PubMed Scopus (1) Google A. of and anaemia after a 2022; PubMed Scopus (0) Google Scholar that may be in can or and of and J Exp Scholar use of inhibitors may iron in iron-deficiency et use of inhibitors and iron in renal transplant 2019; PubMed Scopus Google Scholar associated with anemia in are N. et al.Posttransplantation anemia in renal allograft recipients: prevalence and 2006; PubMed Scopus Google Scholar After by The of the in the of J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar M. T. of early PubMed Google Scholar and et the of iron and iron in J 54: PubMed Scopus Google Scholar the to may be in the general J. of inhibitors on erythropoietin in J PubMed Google Scholar may a in patients with et effects of and inhibitors on erythropoietin in J Nephrol. PubMed Scopus Google Scholar by inhibitors is in the treatment of posttransplant C. et and management of anemia in renal transplant recipients: a European J Transplant. Full Text Full Text PDF PubMed Scopus Google Posttransplant Full Text Full Text PDF PubMed Scopus Google Scholar indicate that with anemia may a decline in a retrospective at with at 6 patients with late posttransplant anemia a decline of whereas patients anemia reported of A. Ayalon-Dangur I. Cooper L. et al.Posttransplantation anemia in kidney transplant recipients: a retrospective cohort study.Medicine. 2017; 96e7735https://doi.org/10.1097/MD.0000000000007735Crossref PubMed Scopus (19) Google Scholar The the association posttransplant anemia and decline, particularly the of anemia correction on the decline is further in the on ESA A the of anemia on graft and reported a association anemia and graft N. L. E. of anemia on patient and graft after kidney a Transplant. PubMed Scopus (19) Google Scholar as by several A. Gafter-Gvili A. Shepshelovich D. et al.Post renal transplantation anemia: causes, severity and their association with graft and patient survival.BMC Nephrol. 2019; 20: 51https://doi.org/10.1186/s12882-019-1244-yCrossref PubMed Scopus (21) Google A. Ayalon-Dangur I. Cooper L. et al.Posttransplantation anemia in kidney transplant recipients: a retrospective cohort study.Medicine. 2017; 96e7735https://doi.org/10.1097/MD.0000000000007735Crossref PubMed Scopus (19) Google R. C. A. et at after kidney transplantation has a long-term on graft and patient Proc. PubMed Google Scholar, Anemia at is risk factor of graft Nephrol. PubMed Scopus Google Scholar, N. J. et and of posttransplant anemia with and cardiovascular outcomes kidney transplant Transplant. PubMed Scopus (0) Google Scholar a time of with early and late anemia reported a higher of graft at than patients A. Ayalon-Dangur I. Cooper L. et al.Posttransplantation anemia in kidney transplant recipients: a retrospective cohort study.Medicine. 2017; 96e7735https://doi.org/10.1097/MD.0000000000007735Crossref PubMed Scopus (19) Google Scholar a cohort of a of the of anemia of associated with graft failure, the association for A. Gafter-Gvili A. Shepshelovich D. et al.Post renal transplantation anemia: causes, severity and their association with graft and patient survival.BMC Nephrol. 2019; 20: 51https://doi.org/10.1186/s12882-019-1244-yCrossref PubMed Scopus (21) Google Scholar A retrospective of the association graft and in the after than at specific time that with no in at reported increased risk of graft of the be that the of the with the A. T. et of hemoglobin is associated with reduced graft after kidney Transplant. 2022; PubMed Scopus (0) Google Scholar disease is frequent after and is the of A. risk in kidney Full Text Full Text PDF PubMed Scopus Google Scholar Anemia is a risk factor for in F. G. 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Cooper L. et al.Posttransplantation anemia in kidney transplant recipients: a retrospective cohort study.Medicine. 2017; 96e7735https://doi.org/10.1097/MD.0000000000007735Crossref PubMed Scopus (19) Google Scholar the association of posttransplant anemia with These retrospective with a of W.C. Chandraker A. Alan Brookhart M. Kramar R. Sunder-Plassmann G. A prospective study of anaemia and long-term outcomes in kidney transplant recipients.Nephrol Dial Transplant. 2006; 21: 3559-3566Crossref PubMed Scopus (57) Google Scholar and the at T. L. et transplantation anemia at risk and on clinical Nephrol. PubMed Scopus (17) Google Scholar and a prospective cohort study with a of to 6 et is a of graft but cardiovascular and in renal transplant recipients: from the Transplant. 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Google Scholar experiencing anemia months posttransplant to targeting of or to no T. M. R. posttransplant anemia with erythropoietin quality of life but of chronic kidney Transplant. PubMed Scopus Google Scholar After higher in the whereas the and of the with ESA quality of life T. M. R. posttransplant anemia with erythropoietin quality of life but of chronic kidney Transplant. PubMed Scopus Google Scholar late posttransplant anemia, the of Anemia and of Renal in Transplant patients study the on graft and quality of life of levels of correction by G. N. et of transplant anemia of allograft Nephrol. PubMed Scopus Google Scholar The a reduced decline in in the correction of to kidney failure, and higher graft survival. The quality of life in the G. N. et of transplant anemia of allograft Nephrol. PubMed Scopus Google Scholar et M. T. 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N. et of hemoglobin levels on long-term kidney function in kidney transplant recipients: a Dial Transplant. 2019; PubMed Scopus Google Scholar The study by et no increased of in to the Ichimaru N. et anemia and supplementation in kidney transplant recipients: a clinical PubMed Scopus Google Scholar Moreover, no adverse cardiovascular effects or in a in with of T. M. R. posttransplant anemia with erythropoietin quality of life but of chronic kidney Transplant. PubMed Scopus Google Scholar The apparent the with and may be by the allograft and are and G. N. et of transplant anemia of allograft Nephrol. PubMed Scopus Google Scholar a chronic allograft kidney may to the kidney of a patient with and M. T. N. et of hemoglobin levels on long-term kidney function in kidney transplant recipients: a Dial Transplant. 2019; PubMed Scopus Google Scholar The suggests that the use of ESA in is safe and associated with a possible favorable of ESA in anemia, although ESAs may be in whereas there is no or for ESA The optimal use of ESA from the of and further is common in KTRs, particularly in the months after C. et and management of anemia in renal transplant recipients: a European J Transplant. Full Text Full Text PDF PubMed Scopus Google E. D. L. et is associated with increased risk of transplant a 2022; PubMed Scopus Google Scholar However, a study than reported association early and transplant as graft or with a E. D. L. et is associated with increased risk of transplant a 2022; PubMed Scopus Google Scholar from associated with reduced graft and increased risk of and at E. of early after kidney transplantation on the clinical outcomes and allograft PubMed Scopus (0) Google Scholar may a to R. et of with in a PubMed Scopus Google Scholar A retrospective cohort study a increased risk with after such as or the risk increased as the number of D. M. A. The association of with in kidney transplant 2022; PubMed Google Scholar in are associated with graft and et and the risk of and graft in kidney transplant recipients.Am J Nephrol. 2017; PubMed Scopus (13) Google Scholar be for posttransplant anemia patients to and on M. Del Vecchio L. Sirolli V. Locatelli F. New treatment approaches for the anemia of CKD.Am J Kidney Dis. 2016; 67: 133-142https://doi.org/10.1053/j.ajkd.2015.06.030Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar The the for use of in KT, the and of anemia correction such as iron or ESA D. M. A. The association of with in kidney transplant 2022; PubMed Google Scholar hypoxia-inducible inhibitors are to anemia in with of the of the in kidney and and to levels and improve iron Anaemia in kidney disease: to Nephrol. PubMed

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