title: Anemia management and chronic renal failure progression.
abstract: Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.
authors.affiliation: Paris-Descartes University School of Medicine, INSERM U652, AP-HP (Hôpital Européen Georges Pompidou), Paris, France. jerome.rossert@egp.aphp.fr
authors.forename: Jerome
authors.initials: J
authors.lastname: Rossert
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.forename: Christian
authors.initials: C
authors.lastname: Jacquot
mesh_terms: D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D017209:Apoptosis; D002986:Clinical Trials as Topic; D003928:Diabetic Nephropathies / Q000503:physiopathology; D018450:Disease Progression; D000068817:Epoetin Alfa; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000502:physiology / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D009399:Nephrons / Q000503:physiopathology; D011446:Prospective Studies; D011485:Protein Binding; D017467:Receptors, Erythropoietin / Q000502:physiology; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa