title: Effect of mycophenolate mofetil on erythropoiesis in stable renal transplant patients is correlated with mycophenolic acid trough levels.
abstract: BACKGROUND
  Both mycophenolate mofetil (MMF) and azathioprine (AZA) are immunosuppressive drugs that inhibit purine synthesis. In theory, MMF selectively inhibits lymphocyte proliferation, while AZA has well-known effects on red blood cells and thrombocytes as well. In renal transplant recipients we replaced CsA therapy by MMF in an attempt to reduce the immunosuppressive load 1 year after kidney transplantation. During this study we observed the effect of MMF on haematological parameters such as haemoglobin (Hb), leukocytes, and thrombocytes.
  
  
  METHODS
  One year after kidney transplantation 26 stable patients were converted from cyclosporin A (CsA) to MMF (2 g/day). Thereafter, these patients were tapered twice in their MMF dose from 2 g to 1.5 g (4 months after conversion) and from 1.5 to 1 g (8 months after conversion) per day. The Hb levels, leukocyte and thrombocyte counts, and mycophenolic acid (MPA) trough levels were routinely measured.
  
  
  RESULTS
  After conversion from CsA to MMF not only creatinine levels and the number of leukocytes, but also the haemoglobin (Hb) level significantly decreased in 21/26 patients (P=0.0004). In eight patients the Hb level dropped more than 1 mmol/l (=1.61 g/dl). Only in two of eight patients was an explanation for blood loss found. The effect on Hb level did not ameliorate after the first MMF dose reduction to 1.5 g/day. After tapering the MMF dose to 1 g/day, the Hb approached the pre-conversion level. Not only the MMF dose but also the mycophenolic acid (MPA) trough level correlated with the Hb level.
  
  
  CONCLUSIONS
  After conversion from CsA to MMF 1 year after kidney transplantation, a decrease in Hb level and leukocyte count was observed. The MPA trough level correlated also with the Hb level. The effect on the Hb level was reversible after dose reduction. This finding suggests that MMF exerts a negative effect on erythropoietic cells.
authors.affiliation: Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: van Besouw
authors.forename: B J
authors.initials: BJ
authors.lastname: van der Mast
authors.forename: P J
authors.initials: PJ
authors.lastname: Smak Gregoor
authors.forename: C J
authors.initials: CJ
authors.lastname: Hesse
authors.forename: J N
authors.initials: JN
authors.lastname: IJzermans
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D001772:Blood Cell Count / Q000187:drug effects; D001792:Blood Platelets / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D019233:Retreatment
chemical_list: D006454:Hemoglobins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid