title: Impaired erythropoietin production in liver transplant recipients: the role of calcineurin inhibitors.
abstract: Anemia is common following liver transplantation. Because cyclosporine inhibits erythropoietin (Epo) production in experimental models, we investigated whether Epo production was impaired in liver transplant recipients receiving a cyclosporine- or tacrolimus-based immunosuppressive regimen. First, serum Epo levels were measured before and 1 year after transplantation in 35 liver transplant recipients. Second, serum Epo levels were compared in a large series of liver transplant recipients with stable graft and renal functions: 27 receiving a cyclosporine-based and 31 receiving a tacrolimus-based immunosuppressive regimen. A reference group was made up of 22 blood donors and 21 nontransplanted subjects with iron-deficiency anemia. Serum Epo levels were significantly lower after than before liver transplantation, especially in cyclosporine-treated patients. Serum Epo concentrations correlated with hematocrit values in both transplant recipients and control subjects. Using multiple linear regression models, the polynomial relationship between hematocrit and serum Epo values was similar to the control group in patients under tacrolimus, whereas Epo production was significantly reduced in patients under cyclosporine-based immunosuppression. Hematocrit values and the type of calcineurin inhibitor were the only parameters independently related to Epo levels. In conclusion, cyclosporine, but not tacrolimus, inhibits Epo production at the doses used in clinical practice.
authors.affiliation: Service d'Hématologie Biologique, Université Paris Descartes, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bardet
authors.forename: Alcindo Pissaia
authors.initials: AP
authors.lastname: Junior
authors.forename: Joël
authors.initials: J
authors.lastname: Coste
authors.forename: Carinne
authors.initials: C
authors.lastname: Lecoq-Lafon
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Denis
authors.initials: D
authors.lastname: Bernard
authors.forename: Olivier
authors.initials: O
authors.lastname: Soubrane
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacombe
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Filoména
authors.initials: F
authors.lastname: Conti
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood; D001782:Blood Donors; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use*; D004921:Erythropoietin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006400:Hematocrit; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011184:Postoperative Period; D011300:Preoperative Care; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D004921:Erythropoietin; D016572:Cyclosporine; D016559:Tacrolimus